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Sample records for acute inflammatory responses

  1. The Acute Inflammatory Response in Trauma / Hemorrhage and ...

    African Journals Online (AJOL)

    Traumatic injury/hemorrhagic shock (T/HS) elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury (TBI). Inflammation is a ...

  2. Systemic inflammatory response following acute traumatic brain injury.

    Science.gov (United States)

    Lu, Jia; Goh, Samantha Jianli; Tng, Priscilla Ying Lei; Deng, Yi Yu; Ling, Eng-Ang; Moochhala, Shabbir

    2009-01-01

    The early, delayed, and systemic effects of acute traumatic brain injury (TBI) are the result of inflammatory mediators which initiate systemic inflammatory response syndrome (SIRS), subsequent complement deficits and coagulopathy. Once SIRS is triggered by acute inflammation, it can detrimentally self-propagate. Systemic inflammation causes tissue damage leading to further inflammation and damage, leaving the body in a vicious cycle of hyperinflammation. Therefore, important inflammatory mediators like interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF) alpha, are targeted in compensatory anti-inflammatory response syndrome (CARS) in an attempt to control the development of SIRS. The hypothalamus-pituitary (HPA)-axis and sympathetic nervous system (SNS) efferent limbs in CARS provide negative feedback for the production of inflammatory mediators. However, in the case of acute TBI, the activation of CARS often leads to the complication of immunosuppression which may result in multi-organ dysfunction syndrome (MODS) and mortality. In light of this, the activation of the SIRS following acute TBI does not bode well. If left uncontrolled, multiple systems will be implicated making it difficult to remedy.

  3. Body mass index mediates inflammatory response to acute dietary challenges.

    Science.gov (United States)

    Matone, Alice; O'Grada, Colm M; Dillon, Eugene T; Morris, Ciara; Ryan, Miriam F; Walsh, Marianne; Gibney, Eileen R; Brennan, Lorraine; Gibney, Michael J; Morine, Melissa J; Roche, Helen M

    2015-11-01

    Acute metabolic challenges provide an opportunity to identify mechanisms of metabolic and nutritional health. In this study, we assessed the transcriptomic response to oral glucose and lipid challenges in a cohort of individuals ranging in age and BMI. The main goal is to identify whether BMI can mediate the metabolic and transcriptional response to dietary challenges, and the differences between lipid and glucose tests. Two hundred fourteen healthy adults were assigned to the challenges and twenty-three individuals were selected for further transcriptomic proofing, using microarray analysis of peripheral blood mononuclear cells. Through linear-mixed models and network analysis, different sets of transcripts and pathways were identified that responded to the challenges depending on BMI. Different transcripts that responded to the lipid and glucose tests, independently of BMI, were also identified. In the network analysis, inflammatory and adhesion processes were strongly represented for both challenges. Our results indicate that BMI is strongly linked to the transcriptomic and metabolic response to acute challenges. The emerging biological processes are mainly inflammation-related pathways, highlighting an interconnection between obesity, inflammation/adhesion, and response to nutritional challenge. The comparison between lipid and glucose challenges shows how these trigger a substantially different molecular response. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Inflammatory biomarkers responses after acute whole body vibration in fibromyalgia

    Directory of Open Access Journals (Sweden)

    V.G.C. Ribeiro

    2018-03-01

    Full Text Available The aims of this study were 1 to characterize the intensity of the vibration stimulation in women diagnosed with fibromyalgia (FM compared to a control group of healthy women (HW matched by age and anthropometric parameters, and 2 to investigate the effect of a single session of whole body vibration (WBV on inflammatory responses. Levels of adipokines, soluble tumor necrosis factor receptors (sTNFr1, sTNFr2, and brain-derived neurotrophic factor (BDNF were determined by enzyme-linked immunosorbent assay. Oxygen consumption (VO2 was estimated by a portable gas analysis system, heart rate (HR was measured using a HR monitor, and perceived exertion (RPE was evaluated using the Borg scale of perceived exertion. Acutely mild WBV increased VO2 and HR similarly in both groups. There was an interaction (disease vs vibration in RPE (P=0.0078, showing a higher RPE in FM compared to HW at rest, which further increased in FM after acute WBV, whereas it remained unchanged in HW. In addition, there was an interaction (disease vs vibration in plasma levels of adiponectin (P=0.0001, sTNFR1 (P=0.000001, sTNFR2 (P=0.0052, leptin (P=0.0007, resistin (P=0.0166, and BDNF (P=0.0179. In conclusion, a single acute session of mild and short WBV can improve the inflammatory status in patients with FM, reaching values close to those of matched HW at their basal status. The neuroendocrine mechanism seems to be an exercise-induced modulation towards greater adaptation to stress response in these patients.

  5. Factors modulating the inflammatory response in acute gouty arthritis

    NARCIS (Netherlands)

    Cleophas, M.C.P.; Crisan, T.O.; Joosten, L.A.B.

    2017-01-01

    PURPOSE OF REVIEW: Gout is a common debilitating form of arthritis and despite our extensive knowledge on the pathogenesis its prevalence is still rising quickly. In the current review, we provide a concise overview of recent discoveries in factors tuning the inflammatory response to soluble uric

  6. Two opposite extremes of adiposity similarly reduce inflammatory response of antigen-induced acute joint inflammation

    NARCIS (Netherlands)

    Oliveira, M.C.; Silveira, A.L.; Tavares, L.P.; Rodrigues, D.F.; Loo, F.A.J. van de; Sousa, L.P.; Teixeira, M.M.; Amaral, F.A.; Ferreira, A.V.

    2017-01-01

    OBJECTIVE: Acute inflammation is a normal response of tissue to an injury. During this process, inflammatory mediators are produced and metabolic alterations occur. Adipose tissue is metabolically activated, and upon food consumption, it disrupts the inflammatory response. However, little is known

  7. The inflammatory response in myocarditis and acute myocardial infarction

    NARCIS (Netherlands)

    Emmens, R.W.

    2016-01-01

    This thesis is about myocarditis and acute myocardial infarction (AMI). These are two cardiac diseases in which inflammation of the cardiac muscle occurs. In myocarditis, inflammation results in the elimination of a viral infection of the heart. During AMI, one of the coronary arteries is occluded,

  8. Myeloid Heme Oxygenase-1 Regulates the Acute Inflammatory Response to Zymosan in the Mouse Air Pouch

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    Rita Brines

    2018-01-01

    Full Text Available Heme oxygenase-1 (HO-1 is induced by many stimuli to modulate the activation and function of different cell types during innate immune responses. Although HO-1 has shown anti-inflammatory effects in different systems, there are few data on the contribution of myeloid HO-1 and its role in inflammatory processes is not well understood. To address this point, we have used HO-1M-KO mice with myeloid-restricted deletion of HO-1 to specifically investigate its influence on the acute inflammatory response to zymosan in vivo. In the mouse air pouch model, we have shown an exacerbated inflammation in HO-1M-KO mice with increased neutrophil infiltration accompanied by high levels of inflammatory mediators such as interleukin-1β, tumor necrosis factor-α, and prostaglandin E2. The expression of the degradative enzyme matrix metalloproteinase-3 (MMP-3 was also enhanced. In addition, we observed higher levels of serum MMP-3 in HO-1M-KO mice compared with control mice, suggesting the presence of systemic inflammation. Altogether, these findings demonstrate that myeloid HO-1 plays an anti-inflammatory role in the acute response to zymosan in vivo and suggest the interest of this target to regulate inflammatory processes.

  9. Flecainide Improve Sepsis Induced Acute Lung Injury by Controlling Inflammatory Response

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    Jia Song

    2016-08-01

    Full Text Available Background: Flecainide is an antiarrhythmic agent that is used primarily in the treatment of cardiac arrhythmias. Some evidences also suggest that flecainide can participate in alveolar fluid clearance and inflammatory responses. This experiment was aimed to evaluate the effects of flecainide on sepsis induced acute lung injury in a rat model. Methods: Rats were treated with subcutaneous infusion of saline or flecainide (0.1 or 0.2 mg/kg/hr by a mini-osmotic pump. Subcutaneous infusion was started 3 hours before and continued until 8 hours after intraperitoneal injection of saline or endotoxin. Animals were sacrificed for analyses of severity of acute lung injury with wet to dry (W/D ratio and lung injury score (LIS in lung and inflammatory responses with level of leukocyte, polymorphonuclear neutrophils (PMNs and inteleukin-8 (IL-8 in bronchoalveolar lavages fluid (BALF. Results: Flecainide markedly improved dose dependently sepsis induced acute lung injury as analysed by W/D ratio (from 2.24 ± 0.11 to 1.76 ± 0.09, p < 0.05 and LIS (from 3 to 1, p < 0.05, and inflammatory response as determined by leukocyte (from 443 ± 127 to 229 ± 95, p < 0.05, PMNs (from 41.43 ± 17.63 to 2.43 ± 2.61, p < 0.05 and IL-8 (from 95.00 ± 15.28 to 40.00 ± 10.21, p < 0.05 in BALF. Conclusions: Flecanide improve sepsis induced acute lung injury in rats by controlling inflammatory responses.

  10. Fibrinogen modulates leukocyte recruitment in vivo during the acute inflammatory response.

    Science.gov (United States)

    Vitorino de Almeida, V; Silva-Herdade, A; Calado, A; Rosário, H S; Saldanha, C

    2015-01-01

    Besides playing an important role in blood hemostases, fibrinogen also regulates leukocyte function in inflammation. Our previous in vitro studies showed that the adhesive behaviour of the neutrophil is modulated by soluble fibrinogen when present at a physiological concentration. This led us to propose that this plasma glycoprotein might further influence leukocyte recruitment in vivo and thus contribute to the inflammatory response. To address this in vivo, leukocyte recruitment was here investigated under acute inflammatory conditions in the absence of soluble fibrinogen in the blood circulation. For such, intravital microscopy on mesentery post-capillary venules was performed on homozygous fibrinogen α chain-deficient mice ((α-/-) mice). Acute inflammatory states were induced by perfusing platelet activating factor (PAF) over the exposed tissue. As control animals, two groups of mice expressing soluble fibrinogen in circulation were used, namely, C57BL/6 wild type animals and heterozygous fibrinogen α chain-deficient mice ((α+/-) mice). Under acute inflammatory conditions, an abnormal pattern of recruitment was observed for leukocytes in homozygous (α-/-) mice in comparison to both control groups. In fact, the former exhibited a significantly decreased number of rolling leukocytes that nevertheless, migrated with increased rolling velocities when compared to leukocytes from control animals. Consistently, homozygous mice further displayed a diminished number of adherent leukocytes than the other groups. Altogether our observations led us to conclude that leukocyte recruitment in homozygous (α-/-) mice is compromised what strongly suggests a role for soluble fibrinogen in leukocyte recruitment in inflammation.

  11. Acute inflammatory responses of nanoparticles in an intra-tracheal instillation rat model.

    Science.gov (United States)

    Armstead, Andrea L; Minarchick, Valerie C; Porter, Dale W; Nurkiewicz, Timothy R; Li, Bingyun

    2015-01-01

    Exposure to hard metal tungsten carbide cobalt (WC-Co) "dusts" in enclosed industrial environments is known to contribute to the development of hard metal lung disease and an increased risk for lung cancer. Currently, the influence of local and systemic inflammation on disease progression following WC-Co exposure remains unclear. To better understand the relationship between WC-Co nanoparticle (NP) exposure and its resultant effects, the acute local pulmonary and systemic inflammatory responses caused by WC-Co NPs were explored using an intra-tracheal instillation (IT) model and compared to those of CeO2 (another occupational hazard) NP exposure. Sprague-Dawley rats were given an IT dose (0-500 μg per rat) of WC-Co or CeO2 NPs. Following 24-hr exposure, broncho-alveolar lavage fluid and whole blood were collected and analyzed. A consistent lack of acute local pulmonary inflammation was observed in terms of the broncho-alveolar lavage fluid parameters examined (i.e. LDH, albumin, and macrophage activation) in animals exposed to WC-Co NP; however, significant acute pulmonary inflammation was observed in the CeO2 NP group. The lack of acute inflammation following WC-Co NP exposure contrasts with earlier in vivo reports regarding WC-Co toxicity in rats, illuminating the critical role of NP dose and exposure time and bringing into question the potential role of impurities in particle samples. Further, we demonstrated that WC-Co NP exposure does not induce acute systemic effects since no significant increase in circulating inflammatory cytokines were observed. Taken together, the results of this in vivo study illustrate the distinct differences in acute local pulmonary and systemic inflammatory responses to NPs composed of WC-Co and CeO2; therefore, it is important that the outcomes of pulmonary exposure to one type of NPs may not be implicitly extrapolated to other types of NPs.

  12. Acute Inflammatory Responses of Nanoparticles in an Intra-Tracheal Instillation Rat Model

    Science.gov (United States)

    Armstead, Andrea L.; Minarchick, Valerie C.; Porter, Dale W.; Nurkiewicz, Timothy R.; Li, Bingyun

    2015-01-01

    Exposure to hard metal tungsten carbide cobalt (WC-Co) “dusts” in enclosed industrial environments is known to contribute to the development of hard metal lung disease and an increased risk for lung cancer. Currently, the influence of local and systemic inflammation on disease progression following WC-Co exposure remains unclear. To better understand the relationship between WC-Co nanoparticle (NP) exposure and its resultant effects, the acute local pulmonary and systemic inflammatory responses caused by WC-Co NPs were explored using an intra-tracheal instillation (IT) model and compared to those of CeO2 (another occupational hazard) NP exposure. Sprague-Dawley rats were given an IT dose (0-500 μg per rat) of WC-Co or CeO2 NPs. Following 24-hr exposure, broncho-alveolar lavage fluid and whole blood were collected and analyzed. A consistent lack of acute local pulmonary inflammation was observed in terms of the broncho-alveolar lavage fluid parameters examined (i.e. LDH, albumin, and macrophage activation) in animals exposed to WC-Co NP; however, significant acute pulmonary inflammation was observed in the CeO2 NP group. The lack of acute inflammation following WC-Co NP exposure contrasts with earlier in vivo reports regarding WC-Co toxicity in rats, illuminating the critical role of NP dose and exposure time and bringing into question the potential role of impurities in particle samples. Further, we demonstrated that WC-Co NP exposure does not induce acute systemic effects since no significant increase in circulating inflammatory cytokines were observed. Taken together, the results of this in vivo study illustrate the distinct differences in acute local pulmonary and systemic inflammatory responses to NPs composed of WC-Co and CeO2; therefore, it is important that the outcomes of pulmonary exposure to one type of NPs may not be implicitly extrapolated to other types of NPs. PMID:25738830

  13. The Systemic Inflammatory Response Syndrome (SIRS) in acutely hospitalised medical patients: a cohort study

    DEFF Research Database (Denmark)

    Comstedt, Pal; Storgaard, Merete; Lassen, Annmarie T

    2009-01-01

    ABSTRACT: BACKGROUND: Sepsis is an infection which has evoked a systemic inflammatory response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS) is identified by two or more symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood leucocyte count. The rel......ABSTRACT: BACKGROUND: Sepsis is an infection which has evoked a systemic inflammatory response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS) is identified by two or more symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood leucocyte count....... The relationship between SIRS symptoms and morbidity and mortality in medical emergency ward patients is unknown. METHODS: We conducted a prospective cohort study of the frequency of SIRS and its relationship to sepsis and death among acutely hospitalised medical patients. In 437 consecutive patients, SIRS status......, blood pressure, infection and comorbidity on admission was registered together with 28-day mortality. RESULTS: A hundred and fifty-four patients (35%) had SIRS on admission, 211 patients (48%) had no SIRS, and 72 patients (16%) had insufficient data to evaluate their SIRS status. SIRS patients were 2...

  14. Acute Inflammatory Response of Patients with Pseudomonas aeruginosa Infections: A Prospective Study.

    Science.gov (United States)

    Gómez-Zorrilla, Silvia; Morandeira, Francisco; Castro, María José; Tubau, Fe; Periche, Elisabet; Cañizares, Rosario; Dominguez, María Angeles; Ariza, Javier; Peña, Carmen

    2017-06-01

    The severity of Pseudomonas aeruginosa (PA) infection may be determined by the interaction with the host immune system. We designed a prospective study to assess the relationship between the inflammatory response and the clinical presentation and outcome of PA infection. We also investigated whether there are differences in the inflammatory response depending on the resistance profile of PA. Interleukin-6 (IL-6), IL-10, procalcitonin (PCT), and C-reactive protein (CRP) were measured. Sixty-nine infection episodes were recorded; 40 caused by non-multidrug-resistant (non-MDR) strains [29 (73%) respiratory; 8 (20%) bacteremia], 12 by MDR non-extensively drug-resistant (MDR-non-XDR) [9 (75%) respiratory; 3 (25%) bacteremia], and 17 by XDR strains [9 (53%) respiratory; 7 (41%) bacteremia]. All inflammatory parameters were significantly higher in patients who developed acute organ dysfunction and bacteremia. PCT levels were higher in patients with early mortality [p = 0.050]. Inflammatory biomarkers were higher in patients with XDR than in those with non-MDR PA [IL-6 430 (67-951) vs. 77 (34-216), p = 0.02; IL-10 3.3 (1.5-16.3) vs. 1.3 (0-3.9), p = 0.02; and PCT 1.1 (0.6-5.2) vs. 0.3 (0.1-1.0), p = 0.008]. The intensity of inflammatory response was associated with the severity of PA infection, particularly if bacteremia occurred. Only PCT was documented useful to predict the outcome. XDR infections presented a higher inflammatory response; related in part to the larger number of bloodstream infections in this group.

  15. The Acute Inflammatory Response to Absorbed Collagen Sponge Is Not Enhanced by BMP-2

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    Hairong Huang

    2017-02-01

    Full Text Available Absorbed collagen sponge (ACS/bone morphogenetic protein-2 (BMP-2 are widely used in clinical practise for bone regeneration. However, the application of this product was found to be associated with a significant pro-inflammatory response, particularly in the early phase after implantation. This study aimed to clarify if the pro-inflammatory activities, associated with BMP-2 added to ACS, were related to the physical state of the carrier itself, i.e., a wet or a highly dehydrated state of the ACS, to the local degree of vascularisation and/or to local biomechanical factors. ACS (0.8 cm diameter/BMP-2 were implanted subcutaneously in the back of 12 eight-week-old Sprague Dawley rats. Two days after surgery, the implanted materials were retrieved and analysed histologically and histomorphometrically. The acute inflammatory response following implantation of ACS was dependent of neither the presence or absence of BMP-2 nor the degree of vascularization in the surrounding tissue nor the hydration state (wet versus dry of the ACS material at the time of implantation. Differential micro biomechanical factors operating at the implantation site appeared to have an influence on the thickness of inflammation. We conclude that the degree of the early inflammatory response of the ACS/BMP-2 may be associated with the physical and chemical properties of the carrier material itself.

  16. The inflammatory response plays a major role in the acute radiation syndrome induced by fission radiation

    International Nuclear Information System (INIS)

    Agay, D.; Chancerelle, Y.; Hirodin, F.; Mathieu, J.; Multon, E.; Van Uye, A.; Mestries, J.C.

    1997-01-01

    At high dose rates, both gamma and neutron irradiation induce an acute inflammatory syndrome with huge intercellular communication disorders. This inflammatory syndrome evolves in two phases, separated by a latency phase. During the prodromal phase, the molecular and cellular lesions induced by free radicals trigger an initial response which associates cellular repair and multicellular interactions involving both humoral and nervous communications. A large part of perturbations constitute a non specific inflammatory syndrome and clinically silent coagulation disorders which are linked by common intercellular mediators. All these perturbations are rapidly reversible and there is no correlation between the radiation dose and the severity of the response. During the manifest-illness phase, both inflammatory and coagulation disorders resume, slightly preceding the clinical symptoms. Biochemical symptoms are moderate in the animals which will survive, but they escape regulatory mechanisms in those which will die, giving rise to a vicious circle. These biochemical disorders are largely responsible for the death. With lower dose rates, it cannot be excluded that great cellular communication disorders take place at the tissue level, with limited blood modifications. This aspect should be taken into account for the optimization of cytokine therapies. (authors)

  17. Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study.

    Science.gov (United States)

    Kaspar, Felix; Jelinek, Herbert F; Perkins, Steven; Al-Aubaidy, Hayder A; deJong, Bev; Butkowski, Eugene

    2016-01-01

    This study compared acute and late effect of single-bout endurance training (ET) and high-intensity interval training (HIIT) on the plasma levels of four inflammatory cytokines and C-reactive protein and insulin-like growth factor 1. Cohort study with repeated-measures design. Seven healthy untrained volunteers completed a single bout of ET and HIIT on a cycle ergometer. ET and HIIT sessions were held in random order and at least 7 days apart. Blood was drawn before the interventions and 30 min and 2 days after the training sessions. Plasma samples were analyzed with ELISA for the interleukins (IL), IL-1β, IL-6, and IL-10, monocyte chemoattractant protein-1 (MCP-1), insulin growth factor 1 (IGF-1), and C-reactive protein (CRP). Statistical analysis was with Wilcoxon signed-rank tests. ET led to both a significant acute and long-term inflammatory response with a significant decrease at 30 minutes after exercise in the IL-6/IL-10 ratio (-20%; p = 0.047) and a decrease of MCP-1 (-17.9%; p = 0.03). This study demonstrates that ET affects the inflammatory response more adversely at 30 minutes after exercise compared to HIIT. However, this is compensated by a significant decrease in MCP-1 at two days associated with a reduced risk of atherosclerosis.

  18. Contribution of leukocytes to the induction and resolution of the acute inflammatory response in chickens.

    Science.gov (United States)

    More Bayona, Juan A; Karuppannan, Anbu Kumar; Barreda, Daniel R

    2017-09-01

    A successful immune response against invading pathogens relies on the efficient activation of host defense mechanisms and a timely return to immune homeostasis. Despite their importance, these mechanisms remain ill-defined in most animal groups. This study focuses on the acute inflammatory response of chickens, important both as an avian model with a unique position in evolution as well as an increasingly notable target of infectious zoonotic diseases. We took advantage of an in vivo self-resolving intra-abdominal challenge model to provide an integrative view of leukocyte responses during the induction and resolution phases of acute inflammation. Our results showed rapid leukocyte infiltration into the abdominal cavity post zymosan challenge (significant increase as early as 4 h), which was dominated by heterophils. Peak leukocyte infiltration and ROS production reached maximum levels at 12 h post challenge, which was significantly earlier than comparative studies in teleost fish and mice. Both heterophils and monocyte/macrophages contributed to ROS production. Local leukocyte infiltration was preceded by an increase in peripheral leukocytes and a drop in the number of bone marrow leukocytes. The proportion of apoptotic leukocytes increased following peak of acute inflammation, rising to significant levels within the abdominal cavity by 48 h, consistent with other indicators for the resolution of inflammation. Importantly, comparison of chicken phagocytic responses with those previously shown in agnathan, teleost and murine models suggested a progressive evolutionary shift towards an increased sensitivity to pro-inflammatory pathogen-derived particles and decreased sensitivity towards homeostatic stimuli. Thus, while significant conservation can be noted across the immune systems of endotherms, this study highlights additional unique features that govern the induction and resolution of acute inflammation in the avian system, which may be relevant to disease

  19. No inflammatory gene-expression response to acute exercise in human Achilles tendinopathy

    DEFF Research Database (Denmark)

    Pingel, Jessica; Fredberg, Ulrich; Mikkelsen, Lone Ramer

    2013-01-01

    Although histology data favour the view of a degenerative nature of tendinopathy, indirect support for inflammatory reactions to loading in affected tendons exists. The purpose of the present study was to elucidate whether inflammatory signalling responses after acute mechanical loading were more...... Germany (600 mg) × 3/day/1 week) group (n = 13) in a double-blinded-fashion. Tendon biopsies were taken from the painful and a healthy region of the same tendon 2 h after 1 h running. Gene-expression of several targets was analysed in the sampled Achilles tendon biopsies. The mRNA for TGF-ß, collagen...

  20. Upregulation of phagocyte-derived catecholamines augments the acute inflammatory response.

    Directory of Open Access Journals (Sweden)

    Michael A Flierl

    Full Text Available Following our recent report that phagocytic cells (neutrophils, PMNs, and macrophages are newly discovered sources of catecholamines, we now show that both epinephrine and norepinephrine directly activate NFkappaB in macrophages, causing enhanced release of proinflammatory cytokines (TNFalpha, IL-1beta, IL-6. Both adrenal-intact (AD+ and adrenalectomized (ADX rodents were used, because ADX animals had greatly enhanced catecholamine release from phagocytes, facilitating our efforts to understand the role of catecholamines released from phagocytes. Phagocytes isolated from adrenalectomized rats displayed enhanced expression of tyrosine-hydroxylase and dopamine-beta-hydroxylase, two key enzymes for catecholamine production and exhibited higher baseline secretion of norepinephrine and epinephrine. The effects of upregulation of phagocyte-derived catecholamines were investigated in two models of acute lung injury (ALI. Increased levels of phagocyte-derived catecholamines were associated with intensification of the acute inflammatory response, as assessed by increased plasma leak of albumin, enhanced myeloperoxidase content in lungs, augmented levels of proinflammatory mediators in bronchoalveolar lavage fluids, and elevated expression of pulmonary ICAM-1 and VCAM-1. In adrenalectomized rats, development of ALI was enhanced and related to alpha(2-adrenoceptors engagement but not to involvement of mineralocorticoid or glucocorticoid receptors. Collectively, these data demonstrate that catecholamines are potent inflammatory activators of macrophages, upregulating NFkappaB and further downstream cytokine production of these cells. In adrenalectomized animals, which have been used to further assess the role of catecholamines, there appears to be a compensatory increase in catecholamine generating enzymes and catecholamines in macrophages, resulting in amplification of the acute inflammatory response via engagement of alpha(2-adrenoceptors.

  1. Allicin enhances host pro-inflammatory immune responses and protects against acute murine malaria infection

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    Feng Yonghui

    2012-08-01

    Full Text Available Abstract Background During malaria infection, multiple pro-inflammatory mediators including IFN-γ, TNF and nitric oxide (NO play a crucial role in the protection against the parasites. Modulation of host immunity is an important strategy to improve the outcome of malaria infection. Allicin is the major biologically active component of garlic and shows anti-microbial activity. Allicin is also active against protozoan parasites including Plasmodium, which is thought to be mediated by inhibiting cysteine proteases. In this study, the immunomodulatory activities of allicin were assessed during acute malaria infection using a rodent malaria model Plasmodium yoelii 17XL. Methods To determine whether allicin modulates host immune responses against malaria infection, mice were treated with allicin after infection with P. yoelii 17XL. Mortality was checked daily and parasitaemia was determined every other day. Pro-inflammatory mediators and IL-4 were quantified by ELISA, while NO level was determined by the Griess method. The populations of dendritic cells (DCs, macrophages, CD4+ T and regulatory T cells (Treg were assessed by FACS. Results Allicin reduced parasitaemia and prolonged survival of the host in a dose-dependent manner. This effect is at least partially due to improved host immune responses. Results showed that allicin treatment enhanced the production of pro-inflammatory mediators such as IFN-γ, TNF, IL-12p70 and NO. The absolute numbers of CD4+ T cells, DCs and macrophages were significantly higher in allicin-treated mice. In addition, allicin promoted the maturation of CD11c+ DCs, whereas it did not cause major changes in IL-4 and the level of anti-inflammatory cytokine IL-10. Conclusions Allicin could partially protect host against P. yoelii 17XL through enhancement of the host innate and adaptive immune responses.

  2. Cold stress aggravates inflammatory responses in an LPS-induced mouse model of acute lung injury

    Science.gov (United States)

    Joo, Su-Yeon; Park, Mi-Ju; Kim, Kyun-Ha; Choi, Hee-Jung; Chung, Tae-Wook; Kim, Yong Jin; Kim, Joung Hee; Kim, Keuk-Jun; Joo, Myungsoo; Ha, Ki-Tae

    2016-08-01

    Although the relationship between environmental cold temperature and susceptibility to respiratory infection is generally accepted, the effect of ambient cold temperature on host reactivity in lung inflammation has not been fully studied. To examine the function of ambient cold temperature on lung inflammation, mice were exposed to 4 °C for 8 h each day for 14 days. In the lungs of mice exposed to cold stress, inflammatory cells in bronchoalveolar lavage (BAL) fluid and lung tissues were slightly increased by about twofold. However, the structures of pulmonary epithelial cells were kept within normal limits. Next, we examined the effect of cold stress on the inflammatory responses in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The infiltration of neutrophils and inflammation of lung tissue determined by histology were significantly increased by exposure to ambient cold temperature. In addition, the production of pro-inflammatory cytokines including interleukin (IL)-12, IL-17, and monokine induced by gamma interferon (MIG) was elevated by exposure to cold stress. Therefore, we suggest that cold stress is a factor that exacerbates lung inflammation including ALI. To our knowledge, this is the first report on the relationship between cold stress and severity of lung inflammation.

  3. Effect of oral mesalamine on inflammatory response in acute uncomplicated diverticulitis.

    Science.gov (United States)

    Nespoli, Luca; Lo Bianco, Giulia; Uggeri, Fabio; Romano, Fabrizio; Nespoli, Angelo; Bernasconi, Davide Paolo; Gianotti, Luca

    2015-07-21

    To evaluate the impact of mesalamine administration on inflammatory response in acute uncomplicated diverticulitis. We conducted a single centre retrospective cohort study on patients admitted to our surgical department between January 2012 and May 2014 with a computed tomography -confirmed diagnosis of acute uncomplicated diverticulitis. A total of 50 patients were included in the analysis, 20 (study group) had received 3.2 g/d of mesalamine starting from the day of admission in addition to the usual standard treatment, 30 (control group) had received standard therapy alone. Data was retrieved from a prospective database. Our primary study endpoints were: C reactive protein mean levels over time and their variation from baseline (ΔCRP) over the first three days of treatment. Secondary end points included: mean white blood cell and neutrophile count over time, time before regaining of regular bowel movements (passing of stools), time before reintroduction of food intake, intensity of lower abdominal pain over time, analgesic consumption and length of hospital stay. Patients characteristics and inflammatory parameters were similar at baseline in the two groups. The evaluation of CRP levels over time showed, in treated patients, a distinct trend towards a faster decrease compared to controls. This difference approached statistical significance on day 2 (mean CRP 6.0 +/- 4.2 mg/dL and 10.0 +/- 6.7 mg/dL respectively in study group vs controls, P = 0.055). ΔCRP evaluation evidenced a significantly greater increment of this inflammatory marker in the control group on day 1 (P = 0.03). A similar trend towards a faster resolution of inflammation was observed evaluating the total white blood cell count. Neutrophile levels were significantly lower in treated patients on day 2 and on day 3 (P diverticulitis.

  4. Functional role of monocytes and macrophages for the inflammatory response in acute liver injury

    Directory of Open Access Journals (Sweden)

    Henning W Zimmermann

    2012-10-01

    Full Text Available Different etiologies such as drug toxicity, acute viral hepatitis B or acetaminophen poisoning can cause acute liver injury (ALI or even acute liver failure (ALF. Excessive cell death of hepatocytes in the liver is known to result in a strong hepatic inflammation. Experimental murine models of liver injury highlighted the importance of hepatic macrophages, so-called Kupffer cells, for initiating and driving this inflammatory response by releasing proinflammatory cytokines and chemokines including tumor necrosis factor (TNF, interleukin-6 (IL-6, IL-1-beta or monocyte chemoattractant protein 1 (MCP-1, CCL2 as well as activating other non-parenchymal liver cells, e.g. endothelial or hepatic stellate cells (HSC. Many of these proinflammatory mediators can trigger hepatocytic cell death pathways, e.g. via caspase activation, but also activate protective signaling pathways, e.g. via nuclear factor kappa B (NF-kB. Recent studies in mice demonstrated that these macrophage actions largely depend on the recruitment of monocytes into the liver, namely of the inflammatory Ly6c+ (Gr1+ monocyte subset as precursors of tissue macrophages. The chemokine receptor CCR2 and its ligand MCP-1/CCL2 promote monocyte subset infiltration upon liver injury. In contrast, the chemokine receptor CX3CR1 and its ligand fractalkine (CX3CL1 are important negative regulators of monocyte infiltration by controlling their survival and differentiation into functionally diverse macrophage subsets upon injury. The recently identified cellular and molecular pathways for monocyte subset recruitment, macrophage differentiation and interactions with other hepatic cell types in the injured liver may therefore represent interesting novel targets for future therapeutic approaches in ALF.

  5. Limited inflammatory response in rats after acute exposure to a silicon carbide nanoaerosol

    Energy Technology Data Exchange (ETDEWEB)

    Laloy, J., E-mail: julie.laloy@unamur.be [University of Namur (UNamur), Department of Pharmacy, Namur Nanosafety Centre (NNC), Namur Research Institute for Life Sciences NARILIS (Belgium); Lozano, O. [University of Namur (UNamur), Research Centre in Physics of Matter and Radiation (PMR), Namur Nanosafety Centre NNC, Namur Research Institute for Life Sciences NARILIS (Belgium); Alpan, L.; Masereel, B. [University of Namur (UNamur), Department of Pharmacy, Namur Nanosafety Centre (NNC), Namur Research Institute for Life Sciences NARILIS (Belgium); Toussaint, O. [University of Namur (UNamur), Laboratory of Cellular Biochemistry and Biology (URBC), Namur Nanosafety Centre NNC, Namur Research Institute for Life Sciences NARILIS (Belgium); Dogné, J. M. [University of Namur (UNamur), Department of Pharmacy, Namur Nanosafety Centre (NNC), Namur Research Institute for Life Sciences NARILIS (Belgium); Lucas, S. [University of Namur (UNamur), Research Centre in Physics of Matter and Radiation (PMR), Namur Nanosafety Centre NNC, Namur Research Institute for Life Sciences NARILIS (Belgium)

    2015-08-15

    Inhalation represents the major route of human exposure to manufactured nanomaterials (NMs). Assessments are needed about the potential risks of NMs from inhalation on different tissues and organs, especially the respiratory tract. The aim of this limited study is to determine the potential acute pulmonary toxicity in rats exposed to a dry nanoaerosol of silicon carbide (SiC) nanoparticles (NPs) in a whole-body exposure (WBE) model. The SiC nanoaerosol is composed of a bimodal size distribution of 92.8 and 480 nm. The exposure concentration was 4.91 mg/L, close to the highest recommended concentration of 5 mg/L by the Organisation for Economic Co-operation and Development. Rats were exposed for 6 h to a stable and reproducible SiC nanoaerosol under real-time measurement conditions. A control group was exposed to the filtered air used to create the nanoaerosol. Animals were sacrificed immediately, 24 or 72 h after exposure. The bronchoalveolar lavage fluid from rat lungs was recovered. Macrophages filled with SiC NPs were observed in the rat lungs. The greatest load of SiC and macrophages filled with SiC were observed on the rat lungs sacrificed 24 h after acute exposure. A limited acute inflammatory response was found up to 24 h after exposure characterized by a lactate dehydrogenase and total protein increase or presence of inflammatory cells in pulmonary lavage. For this study a WBE model has been developed, it allows the simultaneous exposure of six rats to a nanoaerosol and six rats to clean-filtered air. The nanoaerosol was generated using a rotating brush system (RBG-1000) and analyzed with an electrical low pressure impactor in real time.

  6. The Systemic Inflammatory Response Syndrome (SIRS in acutely hospitalised medical patients: a cohort study

    Directory of Open Access Journals (Sweden)

    Storgaard Merete

    2009-12-01

    Full Text Available Abstract Background Sepsis is an infection which has evoked a systemic inflammatory response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS is identified by two or more symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood leucocyte count. The relationship between SIRS symptoms and morbidity and mortality in medical emergency ward patients is unknown. Methods We conducted a prospective cohort study of the frequency of SIRS and its relationship to sepsis and death among acutely hospitalised medical patients. In 437 consecutive patients, SIRS status, blood pressure, infection and comorbidity on admission was registered together with 28-day mortality. Results A hundred and fifty-four patients (35% had SIRS on admission, 211 patients (48% had no SIRS, and 72 patients (16% had insufficient data to evaluate their SIRS status. SIRS patients were 2.2 times more frequently infected, with 66/154 SIRS patients versus 41/211 non-SIRS patients: p Conclusion We found SIRS status on admission to be moderately associated with infection and strongly related to 28-day mortality.

  7. Resveratrol modulates response against acute inflammatory stimuli in aged mouse brain.

    Science.gov (United States)

    Palomera-Ávalos, V; Griñán-Ferré, C; Izquierdo, V; Camins, A; Sanfeliu, C; Canudas, A M; Pallàs, M

    2018-02-01

    With upcoming age, the capability to fight against harmful stimuli decreases and the organism becomes more susceptible to infections and diseases. Here, the objective was to demonstrate the effect of dietary resveratrol in aged mice in potentiating brain defenses against LipoPolySaccharide (LPS). Acute LPS injection induced a strong proinflammatory effect in 24-months-old C57/BL6 mice hippocampi, increasing InterLeukin (Il)-6, Tumor Necrosis Factor-alpha (Tnf-α), Il-1β, and C-X-C motif chemokine (Cxcl10) gene expression levels. Resveratrol induced higher expression in those cytokines regarding to LPS. Oxidative Stress (OS) markers showed not significant changes after LPS or resveratrol, although for resveratrol treated groups a slight increment in most of the parameters studies was observed, reaching signification for NF-kB protein levels and iNOS expression. However, Endoplasmic Reticulum (ER) stress markers demonstrated significant changes in resveratrol-treated mice after LPS treatment, specifically in eIF2α, BIP, and ATF4. Moreover, as described, resveratrol is able to inhibit the mechanistic Target of Rapamycin (mTOR) pathway and this effect could be linked to (eIF2α) phosphorylation and the increase in the expression of the previously mentioned proinflammatory genes as a response to LPS treatment in aged animals. In conclusion, resveratrol treatment induced a different cellular response in aged animals when they encountered acute inflammatory stimuli. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Inflammatory response to acute exposure to welding fumes during the working day

    Directory of Open Access Journals (Sweden)

    Merja Järvelä

    2013-04-01

    Full Text Available Objectives: To investigate cardiorespiratory and inflammatory responses in male workers following exposure to welding fumes and airborne particles in actual workplace conditions. Materials and Methods: We measured blood leukocytes and their differential counts, platelet count, hemoglobin, sensitive C-reactive protein, fibrinogen, E-selectin, IL-(interleukin1β, IL-6, IL-8, tumor necrosis factor alpha (TNF-α and endothelin-1 in blood samples of twenty workers before and after their working day. We also studied peak expiratory flow (PEF, forced expiratory volume in one second (FEV1, and exhaled nitric oxide (NO. We assessed heart rate variability (HRV by obtaining 24-hour ambulatory electrocardiograms. Results: The total blood leukocytes and neutrophils increased after the work shift, whereas IL-1β and E-selectin decreased significantly. There were no tatistically significant changes in exhaled NO, FEV1, PEF or HRV. Conclusion: Occupational exposure to welding fumes and particles caused a slight, acute inflammatory effect estimated based on the increased values of leukocytes and neutrophils in blood and a decrease in the interleukin 1β and E-selectin values, but no changes in the pulmonary function (exhaled NO, FEV1, PEF or HRV during the working day were observed.

  9. The effect of oxandrolone on the endocrinologic, inflammatory, and hypermetabolic responses during the acute phase postburn.

    Science.gov (United States)

    Jeschke, Marc G; Finnerty, Celeste C; Suman, Oscar E; Kulp, Gabriela; Mlcak, Ronald P; Herndon, David N

    2007-09-01

    Postburn long-term oxandrolone treatment improves hypermetabolism and body composition. The effects of oxandrolone on clinical outcome, body composition, endocrine system, and inflammation during the acute phase postburn in a large prospective randomized single-center trial have not been studied. Burned children (n = 235) with >40% total body surface area burn were randomized (block randomization 4:1) to receive standard burn care (control, n = 190) or standard burn care plus oxandrolone for at least 7 days (oxandrolone 0.1 mg/kg body weight q.12 hours p.o, n = 45). Clinical parameters, body composition, serum hormones, and cytokine expression profiles were measured throughout acute hospitalization. Statistical analysis was performed by Student t test, or ANOVA followed by Bonferroni correction with significance accepted at P < 0.05. Demographics and clinical data were similar in both groups. Length of intensive care unit stay was significantly decreased in oxandrolone-treated patients (0.48 +/- 0.02 days/% burn) compared with controls (0.56 +/- 0.02 days/% burn), (P < 0.05). Control patients lost 8 +/- 1% of their lean body mass (LBM), whereas oxandrolone-treated patients had preserved LBM (+9 +/- 4%), P < 0.05. Oxandrolone significantly increased serum prealbumin, total protein, testosterone, and AST/ALT, whereas it significantly decreased alpha2-macroglobulin and complement C3, P < 0.05. Oxandrolone did not adversely affect the endocrine and inflammatory response as we found no significant differences in the hormone panels and cytokine expression profiles. In this large prospective, double-blinded, randomized single-center study, oxandrolone shortened length of acute hospital stay, maintained LBM, improved body composition and hepatic protein synthesis while having no adverse effects on the endocrine axis postburn, but was associated with an increase in AST and ALT.

  10. The Systemic Inflammatory Response Syndrome (SIRS) in acutely hospitalised medical patients: a cohort study.

    Science.gov (United States)

    Comstedt, Pål; Storgaard, Merete; Lassen, Annmarie T

    2009-12-27

    Sepsis is an infection which has evoked a systemic inflammatory response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS) is identified by two or more symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood leucocyte count. The relationship between SIRS symptoms and morbidity and mortality in medical emergency ward patients is unknown. We conducted a prospective cohort study of the frequency of SIRS and its relationship to sepsis and death among acutely hospitalised medical patients. In 437 consecutive patients, SIRS status, blood pressure, infection and comorbidity on admission was registered together with 28-day mortality. A hundred and fifty-four patients (35%) had SIRS on admission, 211 patients (48%) had no SIRS, and 72 patients (16%) had insufficient data to evaluate their SIRS status. SIRS patients were 2.2 times more frequently infected, with 66/154 SIRS patients versus 41/211 non-SIRS patients: p SIRS patients with 15/154 SIRS patients versus 3/211 non-SIRS patients: p = 0.001, RR 6.9 (95% CI 2.0-23.3). Most of the deaths among patients with SIRS occurred among patients with malignant conditions. Septic shock developed in 4/154 (3%) of the patients with SIRS, whereas this occurred in only one of the 211 patients (0.5%) without SIRS on arrival: p = 0.08, RR 5.5 (95% CI 0.6-48.6). We found SIRS status on admission to be moderately associated with infection and strongly related to 28-day mortality.

  11. Immune and inflammatory response in pigs during acute influenza caused by H1N1 swine influenza virus.

    Science.gov (United States)

    Pomorska-Mól, Małgorzata; Markowska-Daniel, Iwona; Kwit, Krzysztof; Czyżewska, Ewelina; Dors, Arkadiusz; Rachubik, Jarosław; Pejsak, Zygmunt

    2014-10-01

    Swine influenza (SI) is an acute respiratory disease of pigs, caused by swine influenza virus (SIV). Little is known about the inflammatory response in the lung during acute SI and its correlation with clinical signs or lung pathology. Moreover, until now there has been a limited amount of data available on the relationship between the concentrations of pro- and anti-inflammatory cytokines in the lungs and the serum concentration of acute-phase proteins (APPs) in SIV-infected pigs. In the present study, the porcine inflammatory and immune responses during acute influenza caused by H1N1 SIV (SwH1N1) were studied. Nine pigs were infected intratracheally, and five served as controls. Antibodies against SIV were measured by haemagglutination inhibition assay, and the influenza-virus-specific T-cell response was measured using a proliferation assay. C-reactive protein (CRP), haptoglobin (Hp), serum amyloid A (SAA), and pig major acute-phase protein (Pig-MAP) the concentrations in serum and concentration of IL-1β, IL-6, IL-8, IL-10, TNF-α and IFN-γ in lung tissues were measured using commercial ELISAs.

  12. The Systemic Inflammatory Response Syndrome (SIRS) in acutely hospitalised medical patients: a cohort study

    OpenAIRE

    Storgaard Merete; Comstedt Pål; Lassen Annmarie T

    2009-01-01

    Abstract Background Sepsis is an infection which has evoked a systemic inflammatory response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS) is identified by two or more symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood leucocyte count. The relationship between SIRS symptoms and morbidity and mortality in medical emergency ward patients is unknown. Methods We conducted a prospective cohort study of the frequency of SIRS and its relationship t...

  13. Transcompartmental Inflammatory Responses in Humans

    DEFF Research Database (Denmark)

    Plovsing, Ronni R; Berg, Ronan M G; Evans, Kevin A

    2014-01-01

    OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following lipopolysacchar......OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following...

  14. Mechanism of cigarette smoke condensate-induced acute inflammatory response in human bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Mohapatra Shyam S

    2002-07-01

    Full Text Available Abstract Background To demonstrate the involvement of tobacco smoking in the pathophysiology of lung disease, the responses of pulmonary epithelial cells to cigarette smoke condensate (CSC — the particulate fraction of tobacco smoke — were examined. Methods The human alveolar epithelial cell line A549 and normal human bronchial epithelial cells (NHBEs were exposed to 0.4 μg/ml CSC, a concentration that resulted in >90% cell survival and Results NHBEs exposed to CSC showed increased expression of the inflammatory mediators sICAM-1, IL-1β, IL-8 and GM-CSF, as determined by RT-PCR. CSC-induced IL-1β expression was reduced by PD98059, a blocker of mitogen-actived protein kinase (MAPK kinase (MEK, and by PDTC, a NFκB inhibitor. Analysis of intracellular signaling pathways, using antibodies specific for phosphorylated MAPKs (extracellular signal-regulated kinase [ERK]-1/2, demonstrated an increased level of phosphorylated ERK1/2 with increasing CSC concentration. Nuclear localization of phosphorylated ERK1/2 was seen within 30 min of CSC exposure and was inhibited by PD98059. Increased phosphorylation and nuclear translocation of IκB was also seen after CSC exposure. A549 cells transfected with a luciferase reporter plasmid containing a NFκB-inducible promoter sequence and exposed to CSC (0.4 μg/ml or TNF-α (50 ng/ml had an increased reporter activity of approximately 2-fold for CSC and 3.5-fold for TNF-α relative to untreated controls. Conclusion The acute phase response of NHBEs to cigarette smoke involves activation of both MAPK and NFκB.

  15. Vitamin D3 pretreatment regulates renal inflammatory responses during lipopolysaccharide-induced acute kidney injury.

    Science.gov (United States)

    Xu, Shen; Chen, Yuan-Hua; Tan, Zhu-Xia; Xie, Dong-Dong; Zhang, Cheng; Zhang, Zhi-Hui; Wang, Hua; Zhao, Hui; Yu, De-Xin; Xu, De-Xiang

    2015-12-22

    Vitamin D receptor (VDR) is highly expressed in human and mouse kidneys. Nevertheless, its functions remain obscure. This study investigated the effects of vitamin D3 (VitD3) pretreatment on renal inflammation during lipopolysaccharide (LPS)-induced acute kidney injury. Mice were intraperitoneally injected with LPS. In VitD3 + LPS group, mice were pretreated with VitD3 (25 μg/kg) at 48, 24 and 1 h before LPS injection. As expected, an obvious reduction of renal function and pathological damage was observed in LPS-treated mice. VitD3 pretreatment significantly alleviated LPS-induced reduction of renal function and pathological damage. Moreover, VitD3 pretreatment attenuated LPS-induced renal inflammatory cytokines, chemokines and adhesion molecules. In addition, pretreatment with 1,25(OH)2D3, the active form of VitD3, alleviated LPS-induced up-regulation of inflammatory cytokines and chemokines in human HK-2 cells, a renal tubular epithelial cell line, in a VDR-dependent manner. Further analysis showed that VitD3, which activated renal VDR, specifically repressed LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit in the renal tubules. LPS, which activated renal NF-κB, reciprocally suppressed renal VDR and its target gene. Moreover, VitD3 reinforced the physical interaction between renal VDR and NF-κB p65 subunit. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity during LPS-induced acute kidney injury.

  16. Influence of sex and developmental stage on acute hepatotoxic and inflammatory responses to liver procarcinogens in the mouse

    International Nuclear Information System (INIS)

    Hanna, Daniel; Riedmaier, Ariane Emami; Sugamori, Kim S.; Grant, Denis M.

    2016-01-01

    The incidence of liver cancer is higher in men than in women. This sex difference is also observed in murine tumor induction models that result in the appearance of liver tumors in adult mice following their exposure on postnatal days 8 and/or 15 to carcinogens such as 4-aminobiphenyl (ABP) or diethylnitrosamine (DEN). Previous studies performed in adult mice showed that acute hepatotoxic and inflammatory responses to high-dose DEN exposure were greater in males than in females, leading to the suggestion that these responses could account for the sex difference in tumor development. We also recently observed that female but not male mice exposed postnatally to ABP had slightly increased expression of the antioxidant defense genes Nqo1 and Ggt1, which are regulated by the oxidative stress response protein nuclear factor erythroid 2-related factor 2 (NRF2), while expression of Hmox1 was increased in both sexes. The goal of the present study was therefore to compare selected acute hepatotoxic, inflammatory and oxidative stress defense responses to ABP, DEN, or the prototype hepatotoxicant carbon tetrachloride (CCl 4 ), in male and female mice exposed to these chemicals either postnatally or as adults. Exposure of adult mice to ABP, DEN or CCl 4 produced a 2-fold greater acute elevation in serum levels of the hepatotoxicity biomarker alanine aminotransferase (ALT) in males than in females, while levels of the inflammatory biomarker interleukin-6 (IL-6) showed no sex difference. However, treatment of immature mice with either ABP or DEN using standard tumor-inducing postnatal exposure protocols produced no increase in serum ALT or IL-6 levels in either males or females, while CCl 4 produced a 40-fold ALT elevation but with no sex difference. Basal expression of the NRF2-responsive gene Nqo1 was higher in adult females than in males, but there was no sex difference in basal expression of Ggt1 or Hmox1. Sexually immature animals showed no sex difference in basal

  17. The acute-phase response and serum amyloid A inhibit the inflammatory response to Acinetobacter baumannii Pneumonia

    NARCIS (Netherlands)

    Renckens, Rosemarijn; Roelofs, Joris J. T. H.; Knapp, Sylvia; de Vos, Alex F.; Florquin, Sandrine; van der Poll, Tom

    2006-01-01

    BACKGROUND: Acinetobacter baumannii is an emerging pathogen in nosocomial pneumonia. Trauma and postsurgical patients display a profound acute-phase protein response and are susceptible to pneumonia. METHODS: To study the way in which the acute-phase response induced by sterile tissue injury

  18. Characterization of the acute inflammatory response in the hybrid tambacu (Piaractus mesopotamicus male x Colossoma macropomum female) (Osteichthyes).

    Science.gov (United States)

    Martins, M L; Myiazaki, D M Y; Tavares-Dias, M; Fenerick, J; Onaka, E M; Bozzo, F R; Fujimoto, R Y; Moraes, F R

    2009-08-01

    This work evaluated the acute inflammatory response induced by injections of 0.5 mL saline solution (control), 500 microg carrageenin and 0.5 mL thioglycollate 3% in the swim bladder of juvenile tambacu hybrid. Fish were distributed in three treatments, three replications and acclimated for a period of 10 days before assay. The cell characterization from the inflammatory exudate was performed in Giemsa and PAS stained smears. Carrageenin, injected in fish, showed an increase on the total number of cells in the inflammatory exudate when compared to saline and thioglycollate injected. Whereas, for carrageenin-injected fish, the percentage of thrombocyte was higher than thioglycollate. On the other hand, granulocyte percentage in thioglycollate-injected fish was higher than the ones injected using carrageenin. Carrageenin provoked the highest migration of macrophage to the inflammatory site. The PAS method confirmed the presence of three types of granulocytes: eosinophilic granular cell (EGC) type 1 with the characteristics of a special granulocytic cell commonly found in the circulating blood; EGC type 2 shorter than the last one and neutrophil. This study contributes to a better understanding of the inflammatory response and infectious processes in native fish.

  19. The Impact of Sleep Restriction and Simulated Physical Firefighting Work on Acute Inflammatory Stress Responses.

    Directory of Open Access Journals (Sweden)

    Alexander Wolkow

    Full Text Available This study investigated the effect restricted sleep has on wildland firefighters' acute cytokine levels during 3 days and 2 nights of simulated physical wildfire suppression work.Firefighters completed multiple days of physical firefighting work separated by either an 8-h (Control condition; n = 18 or 4-h (Sleep restriction condition; n = 17 sleep opportunity each night. Blood samples were collected 4 times a day (i.e., 06:15, 11:30, 18:15, 21:30 from which plasma cytokine levels (IL-6, IL-8, IL-1β, TNF-α, IL-4, IL-10 were measured.The primary findings for cytokine levels revealed a fixed effect for condition that showed higher IL-8 levels among firefighters who received an 8-h sleep each night. An interaction effect demonstrated differing increases in IL-6 over successive days of work for the SR and CON conditions. Fixed effects for time indicated that IL-6 and IL-4 levels increased, while IL-1β, TNF-α and IL-8 levels decreased. There were no significant effects for IL-10 observed.Findings demonstrate increased IL-8 levels among firefighters who received an 8-h sleep when compared to those who had a restricted 4-h sleep. Firefighters' IL-6 levels increased in both conditions which may indicate that a 4-h sleep restriction duration and/or period (i.e., 2 nights was not a significant enough stressor to affect this cytokine. Considering the immunomodulatory properties of IL-6 and IL-4 that inhibit pro-inflammatory cytokines, the rise in IL-6 and IL-4, independent of increases in IL-1β and TNF-α, could indicate a non-damaging response to the stress of simulated physical firefighting work. However, given the link between chronically elevated cytokine levels and several diseases, further research is needed to determine if firefighters' IL-8 and IL-6 levels are elevated following repeated firefighting deployments across a fire season and over multiple fire seasons.

  20. The Impact of Sleep Restriction and Simulated Physical Firefighting Work on Acute Inflammatory Stress Responses.

    Science.gov (United States)

    Wolkow, Alexander; Ferguson, Sally A; Vincent, Grace E; Larsen, Brianna; Aisbett, Brad; Main, Luana C

    2015-01-01

    This study investigated the effect restricted sleep has on wildland firefighters' acute cytokine levels during 3 days and 2 nights of simulated physical wildfire suppression work. Firefighters completed multiple days of physical firefighting work separated by either an 8-h (Control condition; n = 18) or 4-h (Sleep restriction condition; n = 17) sleep opportunity each night. Blood samples were collected 4 times a day (i.e., 06:15, 11:30, 18:15, 21:30) from which plasma cytokine levels (IL-6, IL-8, IL-1β, TNF-α, IL-4, IL-10) were measured. The primary findings for cytokine levels revealed a fixed effect for condition that showed higher IL-8 levels among firefighters who received an 8-h sleep each night. An interaction effect demonstrated differing increases in IL-6 over successive days of work for the SR and CON conditions. Fixed effects for time indicated that IL-6 and IL-4 levels increased, while IL-1β, TNF-α and IL-8 levels decreased. There were no significant effects for IL-10 observed. Findings demonstrate increased IL-8 levels among firefighters who received an 8-h sleep when compared to those who had a restricted 4-h sleep. Firefighters' IL-6 levels increased in both conditions which may indicate that a 4-h sleep restriction duration and/or period (i.e., 2 nights) was not a significant enough stressor to affect this cytokine. Considering the immunomodulatory properties of IL-6 and IL-4 that inhibit pro-inflammatory cytokines, the rise in IL-6 and IL-4, independent of increases in IL-1β and TNF-α, could indicate a non-damaging response to the stress of simulated physical firefighting work. However, given the link between chronically elevated cytokine levels and several diseases, further research is needed to determine if firefighters' IL-8 and IL-6 levels are elevated following repeated firefighting deployments across a fire season and over multiple fire seasons.

  1. Cheongsangbangpung-tang ameliorated the acute inflammatory response via the inhibition of NF-κB activation and MAPK phosphorylation.

    Science.gov (United States)

    Kim, Seon Young; Park, Sang Mi; Hwangbo, Min; Lee, Jong Rok; Byun, Sung Hui; Ku, Sae Kwang; Cho, Il Je; Kim, Sang Chan; Jee, Seon Young; Park, Sook Jahr

    2017-01-13

    Cheongsangbangpung-tang (CBT) is a traditional herbal formula used in Eastern Asia to treat heat-related diseases and swellings in the skin. The present study was conducted to evaluate the anti-inflammatory effects of cheongsangbangpung-tang extract (CBTE) both in vitro and in vivo. The in vitro effects of CBTE on the lipopolysaccharide (LPS)-induced production of inflammation-related proteins were examined in RAW 264.7 cells. The levels of nitric oxide (NO) were measured with the Griess reagent. Inflammatory cytokines and prostaglandin E 2 (PGE 2 ) were detected using the enzyme-linked immunosorbent assay (ELISA) method. Inflammation-related proteins were detected by Western blot. The effect of CBTE on acute inflammation in vivo was evaluated using carrageenan (CA)-induced paw oedema. To evaluate the anti-inflammatory effect, paw oedema volume, thickness of the dorsum and ventrum pedis skin, number of infiltrated inflammatory cells, and number of COX-2-, iNOS-immunoreactive cells were measured. In an in vitro study, CBTE inhibited the production of NO and PGE 2 and also decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) activity, interleukin (IL)-1β, IL-6 and tumuor necrosis factor-α. In LPS-activated macrophages, nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) signalling is a pivotal pathway in the inflammatory process. These plausible molecular mechanisms increased the phosphorylation of I-κBα, while the activation of NF-κB and the phosphorylation of MAPK by LPS were blocked by CBTE treatment. In our in vivo study, a CA-induced acute oedematous paw inflammation rat model was used to evaluate the anti-inflammatory effect of CBTE. CBTE significantly reduced the increases in paw swelling, skin thicknesses, infiltrated inflammatory cells and iNOS-, COX-2 positive cells induced by CA injection. Based on these results, CBTE should favourably inhibit the acute inflammatory response through

  2. Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress

    Science.gov (United States)

    Picard, Martin; McManus, Meagan J.; Gray, Jason D.; Nasca, Carla; Moffat, Cynthia; Kopinski, Piotr K.; Seifert, Erin L.; McEwen, Bruce S.; Wallace, Douglas C.

    2015-01-01

    The experience of psychological stress triggers neuroendocrine, inflammatory, metabolic, and transcriptional perturbations that ultimately predispose to disease. However, the subcellular determinants of this integrated, multisystemic stress response have not been defined. Central to stress adaptation is cellular energetics, involving mitochondrial energy production and oxidative stress. We therefore hypothesized that abnormal mitochondrial functions would differentially modulate the organism’s multisystemic response to psychological stress. By mutating or deleting mitochondrial genes encoded in the mtDNA [NADH dehydrogenase 6 (ND6) and cytochrome c oxidase subunit I (COI)] or nuclear DNA [adenine nucleotide translocator 1 (ANT1) and nicotinamide nucleotide transhydrogenase (NNT)], we selectively impaired mitochondrial respiratory chain function, energy exchange, and mitochondrial redox balance in mice. The resulting impact on physiological reactivity and recovery from restraint stress were then characterized. We show that mitochondrial dysfunctions altered the hypothalamic–pituitary–adrenal axis, sympathetic adrenal–medullary activation and catecholamine levels, the inflammatory cytokine IL-6, circulating metabolites, and hippocampal gene expression responses to stress. Each mitochondrial defect generated a distinct whole-body stress-response signature. These results demonstrate the role of mitochondrial energetics and redox balance as modulators of key pathophysiological perturbations previously linked to disease. This work establishes mitochondria as stress-response modulators, with implications for understanding the mechanisms of stress pathophysiology and mitochondrial diseases. PMID:26627253

  3. Rebound inflammatory response during the acute phase of myocardial infarction after simvastatin withdrawal.

    Science.gov (United States)

    Sposito, Andrei C; Carvalho, Luiz Sergio F; Cintra, Riobaldo M R; Araújo, Ana Laura R; Ono, Andre H; Andrade, Joalbo M; Coelho, Otavio Rizzi; Quinaglia e Silva, Jose C

    2009-11-01

    The present study aimed to verify the existence of a rebound inflammatory effect after statin withdrawal in the acute phase of myocardial infarction (MI). In a prospective observational cohort, changes in C-reactive protein (CRP) between the first and the fifth day after MI were evaluated in 249 consecutive patients who were using statins prior to and during MI (SS), statins prior to but not during MI (SN), no statin prior to but during MI (NS), and no statin prior to nor during MI (NN). Data are presented as median (interquartile range). At baseline, statin users presented a trend to lower CRP values as compared with those without this treatment before the MI (NN: 1.0(0.4-1.5)mg/dL vs. NS: 1.0(0.3-2.8)mg/dL vs. SS: 0.5(0.3-1.0)mg/dL vs. SN: 0.6(0.4-1.0)mg/dL; p=0.08). By the fifth day, median CRP was significantly higher in the SN (18.1(16.1-23.2)mg/dL) group as compared with other groups (NN: 10.5(9.3-13.2)mg/dL vs. NS: 2.9(1.5-4.5)mg/dL vs. SS: 1.1(0.8-2.4)mg/dL; p<0.0001). At the fifth day, the median CRP in the NN group was lower than in the SN group (p<0.0001), but higher than the NS and SS groups (p<0.0001). There was no significant correlation between CRP change and the change of LDL-cholesterol, HDL-cholesterol or triglycerides. The present study has, for the first time, provided evidence for the existence of a rebound inflammatory effect after statin cessation. This rebound reaction may contribute for the adverse outcome of patients who stop statin treatment during MI.

  4. Circadian time-dependent antioxidant and inflammatory responses to acute cadmium exposure in the brain of zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jia-Lang, E-mail: zhengjialang@aliyun.com; Yuan, Shuang-Shuang; Wu, Chang-Wen; Lv, Zhen-Ming; Zhu, Ai-Yi

    2017-01-15

    Highlights: • Gene changed at mRNA, protein and activity levels between exposure time points. • ROS mediated antioxidant and inflammatory responses by Nrf2 and NF-κB. • The effect of time of day on Cd-induced toxicity should not be neglected in fish. - Abstract: Up to date, little information is available on effects of circadian rhythm on metal-induced toxicity in fish. In this study, zebrafish were acutely exposed to 0.97 mg L{sup −1} cadmium for 12 h either at ZT0 (the light intensity began to reached maximum) or at ZT12 (light intensity began to reached minimum) to evaluate the temporal sensitivity of oxidative stress and inflammatory responses in the brain of zebrafish. Profiles of responses of some genes at mRNA, protein and activity levels were different between ZT0 and ZT12 in the normal water. Exposure to Cd induced contrary antioxidant responses and similar inflammatory responses between ZT0 and ZT12. However, the number of inflammatory genes which were up-regulated was significantly greater at ZT12 than at ZT0. And, the up-regulated inflammatory genes were more responsive at ZT12 than at ZT0. At ZT12, antioxidant genes were down-regulated at mRNA, protein and activity levels. Contrarily, antioxidant genes were not affected at mRNA levels but activated at the protein and/or activity levels at ZT0. Reactive oxygen species (ROS) sharply increased and remained relatively stable when fish were exposed to Cd at ZT12 and ZT0, respectively. Positive correlations between ROS levels and mRNA levels of nuclear transcription factor κB (NF-κB) and between mRNA levels of NF-κB and its target genes were observed, suggesting that ROS may play an essential role in regulating the magnitude of inflammatory responses. Taken together, oxidative stress and immunotoxicity in the brain were more serious when fish were exposed to Cd in the evening than in the morning, highlighting the importance of circadian rhythm in Cd-induced neurotoxicity in fish.

  5. Amelioration of Acute Kidney Injury in Lipopolysaccharide-Induced Systemic Inflammatory Response Syndrome by an Aldose Reductase Inhibitor, Fidarestat

    Science.gov (United States)

    Takahashi, Kazunori; Mizukami, Hiroki; Kamata, Kosuke; Inaba, Wataru; Kato, Noriaki; Hibi, Chihiro; Yagihashi, Soroku

    2012-01-01

    Background Systemic inflammatory response syndrome is a fatal disease because of multiple organ failure. Acute kidney injury is a serious complication of systemic inflammatory response syndrome and its genesis is still unclear posing a difficulty for an effective treatment. Aldose reductase (AR) inhibitor is recently found to suppress lipopolysaccharide (LPS)-induced cardiac failure and its lethality. We studied the effects of AR inhibitor on LPS-induced acute kidney injury and its mechanism. Methods Mice were injected with LPS and the effects of AR inhibitor (Fidarestat 32 mg/kg) before or after LPS injection were examined for the mortality, severity of renal failure and kidney pathology. Serum concentrations of cytokines (interleukin-1β, interleukin-6, monocyte chemotactic protein-1 and tumor necrosis factor-α) and their mRNA expressions in the lung, liver, spleen and kidney were measured. We also evaluated polyol metabolites in the kidney. Results Mortality rate within 72 hours was significantly less in LPS-injected mice treated with AR inhibitor both before (29%) and after LPS injection (40%) than untreated mice (90%). LPS-injected mice showed marked increases in blood urea nitrogen, creatinine and cytokines, and AR inhibitor treatment suppressed the changes. LPS-induced acute kidney injury was associated with vacuolar degeneration and apoptosis of renal tubular cells as well as infiltration of neutrophils and macrophages. With improvement of such pathological findings, AR inhibitor treatment suppressed the elevation of cytokine mRNA levels in multiple organs and renal sorbitol accumulation. Conclusion AR inhibitor treatment ameliorated LPS-induced acute kidney injury, resulting in the lowered mortality. PMID:22253906

  6. Plasticity of the systemic inflammatory response to acute infection during critical illness: development of the riboleukogram.

    Directory of Open Access Journals (Sweden)

    Jonathan E McDunn

    2008-02-01

    Full Text Available Diagnosis of acute infection in the critically ill remains a challenge. We hypothesized that circulating leukocyte transcriptional profiles can be used to monitor the host response to and recovery from infection complicating critical illness.A translational research approach was employed. Fifteen mice underwent intratracheal injections of live P. aeruginosa, P. aeruginosa endotoxin, live S. pneumoniae, or normal saline. At 24 hours after injury, GeneChip microarray analysis of circulating buffy coat RNA identified 219 genes that distinguished between the pulmonary insults and differences in 7-day mortality. Similarly, buffy coat microarray expression profiles were generated from 27 mechanically ventilated patients every two days for up to three weeks. Significant heterogeneity of VAP microarray profiles was observed secondary to patient ethnicity, age, and gender, yet 85 genes were identified with consistent changes in abundance during the seven days bracketing the diagnosis of VAP. Principal components analysis of these 85 genes appeared to differentiate between the responses of subjects who did versus those who did not develop VAP, as defined by a general trajectory (riboleukogram for the onset and resolution of VAP. As patients recovered from critical illness complicated by acute infection, the riboleukograms converged, consistent with an immune attractor.Here we present the culmination of a mouse pneumonia study, demonstrating for the first time that disease trajectories derived from microarray expression profiles can be used to quantitatively track the clinical course of acute disease and identify a state of immune recovery. These data suggest that the onset of an infection-specific transcriptional program may precede the clinical diagnosis of pneumonia in patients. Moreover, riboleukograms may help explain variance in the host response due to differences in ethnic background, gender, and pathogen. Prospective clinical trials are indicated

  7. Peripheral Inflammatory Markers and Antioxidant Response during the post-acute and chronic phase after Severe Traumatic Brain Injury

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    Federico Licastro

    2016-11-01

    Full Text Available Traumatic brain injury (TBI is a mechanical insult to the brain caused by external forces and associated with inflammation and oxidative stress. The patients may show different profiles of neurological recovery and a combination of oxidative damage and inflammatory processes can affect their courses. It is known that an over-expression of cytokines can be seen in peripheral blood in the early hours/days after the injury, but little is known about the weeks and months encompassing the post-acute and chronic phases. In addition, no information is available about the antioxidant responses mediated by the major enzymes that regulate ROS levels: superoxide dismutase (SOD, catalase (CAT, peroxidases, and GSH related enzymes. This study investigates the 6-month trends of inflammatory markers and antioxidant responses in 22 severe TBI patients with prolonged disorders of consciousness, consecutively recruited in a dedicated neuro-rehabilitation facility. Patients with a high degree of neurological impairment often show an uncertain outcome. In addition, the profiles of plasma activities were related to the neurological recovery after 12 months.Venous peripheral blood samples were taken blindly as soon as clinical signs and laboratory markers confirmed the absence of infections, 3 and 6 months later. The clinical and neuropsychological assessment continued up to 12 months. Nineteen patients completed the follow up. In the chronic phase, persistent high plasma levels of cytokines can interfere with cognitive functioning and higher post-acute levels of cytokines (IFN-g, TNF-a, IL1b, IL6 are associated with poorer cognitive recoveries 12 months later. Moreover, higher IFN- γ, higher TNF-α and lower glutathione peroxidase (GPx activity are associated with greater disability.The results add evidence of persistent inflammatory response, provide information about long-term imbalance of antioxidant activity and suggest that the over-production of cytokines and

  8. Co-ordinate but disproportionate activation of apoptotic, regenerative and inflammatory pathways characterizes the liver response to acute amebic infection.

    Science.gov (United States)

    Pelosof, Lorraine C; Davis, Paul H; Zhang, Zhi; Zhang, Xiaochun; Stanley, Samuel L

    2006-03-01

    The liver has the remarkable ability to respond to injury with repair and regeneration. The protozoan parasite Entamoeba histolytica is the major cause of liver abscess worldwide. We report a transcriptional analysis of the response of mouse liver to E. histolytica infection, the first study looking at acute liver infection by a non-viral pathogen. Focusing on early time points, we identified 764 genes with altered transcriptional levels in amebic liver abscess. The response to infection is rapid and complex, with concurrent increased expression of genes linked to host defence through IL-1, TLR2, or interferon-induced pathways, liver regeneration via activation of IL-6 pathways, and genes associated with programmed cell death possibly through TNFalpha or Fas pathways. A comparison of amebic liver infection with the liver response to partial hepatectomy or toxins reveals striking similarities between amebic liver abscess and non-infectious injury in key components of the liver regeneration pathways. However, the response in amebic liver abscess is biased towards apoptosis when compared with acute liver injury from hepatectomy, toxins, or other forms of liver infection. E. histolytica infection of the liver simultaneously activates inflammatory, regenerative and apoptotic pathways, but the sum of these early responses is biased towards programmed cell death.

  9. Does chronic physical activity level modify the airway inflammatory response to an acute bout of exercise in the postprandial period?

    Science.gov (United States)

    Kurti, Stephanie P; Rosenkranz, Sara K; Chapes, Stephen K; Teeman, Colby S; Cull, Brooke J; Emerson, Sam R; Levitt, Morton H; Smith, Joshua R; Harms, Craig A

    2017-02-01

    Recent studies have confirmed that a single high-fat meal (HFM) leads to increased airway inflammation. However, exercise is a natural anti-inflammatory and may modify postprandial airway inflammation. The postprandial airway inflammatory response is likely to be modified by chronic physical activity (PA) level. This study investigated whether chronic PA modifies the airway inflammatory response to an acute bout of exercise in the postprandial period in both insufficiently active and active subjects. Thirty-nine nonasthmatic subjects (20 active, 13 males/7 females) who exceeded PA guidelines (≥150 min moderate-vigorous PA/week) and 19 insufficiently active (6 males/13 females) underwent an incremental treadmill test to exhaustion to determine peak oxygen uptake. Subjects were then randomized to a condition (COND), either remaining sedentary (CON) or exercising (EX) post-HFM. Exercise was performed at the heart rate corresponding to 60% peak oxygen uptake on a treadmill for 1 h post-HFM (63% fat, 10 kcal/kg body weight). Blood lipids and exhaled nitric oxide (eNO: marker of airway inflammation) were measured at baseline and 2 h and 4 h post-HFM. Sputum differential cell counts were performed at baseline and 4 h post-HFM. The mean eNO response for all groups increased at 2 h post-HFM (∼6%) and returned to baseline by 4 h (p = 0.03). There was a time × COND interaction (p = 0.04), where EX had a greater eNO response at 4 h compared with CON. Sputum neutrophils increased at 4 h post-HFM (p postprandial period, regardless of habitual activity level.

  10. The inflammatory response in blood and in remote organs following acute kidney injury

    DEFF Research Database (Denmark)

    Brøchner, Anne Craveiro; Dagnaes-Hansen, Frederik; Højberg-Holm, Jimmy

    2014-01-01

    was that elevated levels of cytokines would be found in both blood and in organs distant to the kidneys. Forty mice were divided into five groups. The mice were subjected to the following operations: A: Sham only, no lipopolysaccharide (LPS); B: I/R of both kidneys + LPS; C: LPS only; D: Nephrectomy + LPS; E: I...... infiltration of distant organs measured by the levels of MPO in the lung and liver also showed a significantly higher level in renal I/R compared to hind leg I/R. Renal I/R is associated with a more pronounced inflammatory response in blood and distant organs. The high cytokine levels measured following....../R of both hind legs + LPS. In groups B and E, I/R times were identical. All mice were kept alive for 24 h and then sacrificed. Levels of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α were measured in the blood. The activity of myeloperoxidase (MPO) in lungs, kidneys, and liver was evaluated...

  11. Transcompartmental Inflammatory Responses in Humans

    DEFF Research Database (Denmark)

    Plovsing, Ronni R; Berg, Ronan M G; Evans, Kevin A

    2014-01-01

    OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following...... lipopolysaccharide-induced pulmonary and systemic inflammation. DESIGN: Randomized, double-blind, placebo-controlled, crossover study. SETTING ICU SUBJECTS: Healthy male volunteers. INTERVENTIONS: Fifteen volunteers (mean age, 23; SD, 2 yr) received Escherichia coli endotoxin (lipopolysaccharide, 4 ng/kg) IV...... measured. MEASUREMENTS AND MAIN RESULTS: IV endotoxin elicited a systemic inflammatory response with a time-dependent increase and peak in tumor necrosis factor-α, interleukin-6, and leukocyte counts (all p

  12. Effect of acute intradialytic strength physical exercise on oxidative stress and inflammatory responses in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Marta Esgalhado

    2015-03-01

    Conclusion: These data suggest that acute intradialytic strength physical exercise was unable to reduce oxidative stress and inflammation, and in addition, it seems to reduce plasma SOD levels, which could exacerbate the oxidative stress in HD patients.

  13. Short-Term High- and Moderate-Intensity Training Modifies Inflammatory and Metabolic Factors in Response to Acute Exercise

    Directory of Open Access Journals (Sweden)

    Fabio Santos Lira

    2017-10-01

    Full Text Available Purpose: To compare the acute and chronic effects of high intensity intermittent training (HIIT and steady state training (SST on the metabolic profile and inflammatory response in physically active men.Methods: Thirty recreationally active men were randomly allocated to a control group (n = 10, HIIT group (n = 10, or SST group (n = 10. For 5 weeks, three times per week, subjects performed HIIT (5 km 1-min at 100% of maximal aerobic speed interspersed by 1-min passive recovery or SST (5 km at 70% of maximal aerobic speed while the control group did not perform training. Blood samples were collected at fasting (~12 h, pre-exercise, immediately post, and 60 min post-acute exercise session (pre- and post-5 weeks training. Blood samples were analyzed for glucose, non-ester fatty acid (NEFA, and cytokine (IL-6, IL-10, and TNF-α levels through a three-way analysis (group, period, and moment of measurement with repeated measures in the second and third factors.Results: The results showed an effect of moment of measurement (acute session with greater values to TNF-α and glucose immediately post the exercise when compared to pre exercise session, independently of group or training period. For IL-6 there was an interaction effect for group and moment of measurement (acute session the increase occurred immediately post-exercise session and post-60 min in the HIIT group while in the SST the increase was observed only 60 min post, independently of training period. For IL-10, there was an interaction for training period (pre- and post-training and moment of measurement (acute session, in which in pre-training, pre-exercise values were lower than immediately and 60 min post-exercise, in post-training period pre-exercise values were lower than immediately post-exercise and immediately post-exercise lower than 60 min post, it was also observed that values immediately post-exercise were lower pre- than post-training, being all results independently of intensity

  14. Effects of dexamethasone on intercellular adhesion molecule 1 expression and inflammatory response in necrotizing acute pancreatitis in rats.

    Science.gov (United States)

    Ramudo, Laura; Yubero, Sara; Manso, Manuel A; Sanchez-Recio, Javier; Weruaga, Eduardo; De Dios, Isabel

    2010-10-01

    Adhesion molecules are involved in the inflammatory response during acute pancreatitis (AP). We investigated the effect of dexamethasone (Dx) on intercellular adhesion molecule 1 (ICAM-1) expression during AP and its consequences on leukocyte recruitment and pancreatic damage. Acute pancreatitis was induced in rats by 3.5% sodium taurocholate for 3 hours and 6 hours. Dexamethasone (1 mg/kg) was administered either 30 minutes before or 1 hour after inducing AP. Messenger RNA ICAM-1 expression in pancreas and lung, membrane-bound ICAM-1 in acinar cells, and ICAM-1 plasma levels were analyzed. Histological examination of the pancreas and neutrophil infiltration in pancreas and lung were also measured. Prophylactic and therapeutic administration of Dx down-regulated ICAM-1 expression in pancreas and lung from early AP. Dexamethasone given before AP reduced the pancreatic damage, but lung inflammation was not prevented. Therapeutic Dx treatment was ineffective in avoiding leukocyte recruitment into the pancreas and lung in rats with AP. High ICAM-1 concentration was found in plasma during AP, which was not reduced by Dx treatments. Dexamethasone down-regulates ICAM-1 expression, but it does not completely prevent leukocyte recruitment during sodium taurocholate-induced AP.

  15. Acute inflammatory and anabolic systemic responses to peak and constant-work-rate exercise bout in hospitalized patients with COPD

    OpenAIRE

    Spruit, Martijn A; Troosters, Thierry; Gosselink, Rik; Kasran, Ahmad; Decramer, Marc

    2007-01-01

    Study objectives: To explore the acute systemic inflammatory and anabolic effects of cycling in hospital admitted patients with chronic obstructive pulmonary disease (COPD) and in patients with clinically stable disease. Design: Cross-sectional comparative study. Setting: University Hospital Gasthuisberg, a tertiary care setting. Patients: 16 patients with clinically stable COPD (no acute exacerbation in the past 12 weeks; median age: 73 years (IQR: 60 to 75); median forced expiratory volume ...

  16. Distending Pressure Did Not Activate Acute Phase or Inflammatory Responses in the Airways and Lungs of Fetal, Preterm Lambs.

    Directory of Open Access Journals (Sweden)

    Rebecca Y Petersen

    Full Text Available Mechanical ventilation at birth causes airway injury and lung inflammation in preterm sheep. Continuous positive airway pressure (CPAP is being increasingly used clinically to transition preterm infants at birth.To test if distending pressures will activate acute phase reactants and inflammatory changes in the airways of fetal, preterm lambs.The head and chest of fetal lambs at 128±1 day GA were surgically exteriorized. With placental circulation intact, fetal lambs were then randomized to one of five 15 minute interventions: PEEP of 0, 4, 8, 12, or 16 cmH2O. Recruitment volumes were recorded. Fetal lambs remained on placental support for 30 min after the intervention. The twins of each 0 cmH2O animal served as controls. Fetal lung fluid (FLF, bronchoalveolar lavage fluid (BAL, right mainstem bronchi and peripheral lung tissue were evaluated for inflammation.Recruitment volume increased from 0.4±0.04 mL/kg at 4 cmH2O to 2.4±0.3 mL/kg at 16 cmH2O. The lambs were surfactant deficient, and all pressures were below the opening inflection pressure on pressure-volume curve. mRNA expression of early response genes and pro-inflammatory cytokines did not increase in airway tissue or lung tissue at any pressure compared to controls. FLF and BAL also did not have increases in early response proteins. No histologic changes or Egr-1 activation was present at the pressures used.Distending pressures as high as 16 cmH2O did not recruit lung volume at birth and did not increase markers of injury in the lung or airways in non-breathing preterm fetal sheep.

  17. Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to Residual Oil Fly Ash

    Energy Technology Data Exchange (ETDEWEB)

    Marchini, T.; Magnani, N.D. [Cátedra de Química General e Inorgánica, Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); Paz, M.L. [Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); Vanasco, V. [Cátedra de Química General e Inorgánica, Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); Tasat, D. [CESyMA, Facultad de Ciencia Tecnología, Universidad Nacional de General San Martín, Martín de Irigoyen 3100, 1650 San Martín, Buenos Aires (Argentina); González Maglio, D.H. [Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); and others

    2014-01-15

    It is suggested that systemic oxidative stress and inflammation play a central role in the onset and progression of cardiovascular diseases associated with the exposure to particulate matter (PM). The aim of this work was to evaluate the time changes of systemic markers of oxidative stress and inflammation, after an acute exposure to Residual Oil Fly Ash (ROFA). Female Swiss mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight) or saline solution, and plasma levels of oxidative damage markers [thiobarbituric acid reactive substances (TBARSs) and protein carbonyls], antioxidant status [reduced (GSH) and oxidized (GSSG) glutathione, ascorbic acid levels, and superoxide dismutase (SOD) activity], cytokines levels, and intravascular leukocyte activation were evaluated after 1, 3 or 5 h of exposure. Oxidative damage to lipids and decreased GSH/GSSG ratio were observed in ROFA-exposed mice as early as 1 h. Afterwards, increased protein oxidation, decreased ascorbic acid content and SOD activity were found in this group at 3 h. The onset of an adaptive response was observed at 5 h after the ROFA exposure, as indicated by decreased TBARS plasma content and increased SOD activity. The observed increase in oxidative damage to plasma macromolecules, together with systemic antioxidants depletion, may be a consequence of a systemic inflammatory response triggered by the ROFA exposure, since increased TNF-α and IL-6 plasma levels and polymorphonuclear leukocytes activation was found at every evaluated time point. These findings contribute to the understanding of the increase in cardiovascular morbidity and mortality, in association with environmental PM inhalation. - Highlights: • An acute exposure to ROFA triggers the occurrence of systemic oxidative stress. • Changes in plasmatic oxidative stress markers appear as early as 1 h after exposure. • ROFA induces proinflammatory cytokines release and intravascular leukocyte activation. • PMN

  18. Association of Systemic Inflammatory and Anti-inflammatory Responses with Adverse Outcomes in Acute Pancreatitis: Preliminary Results of an Ongoing Study.

    Science.gov (United States)

    Sharma, Deepesh; Jakkampudi, Aparna; Reddy, Ratnakar; Reddy, Panyala Balakumar; Patil, Aasish; Murthy, H V V; Rao, G Venkat; Reddy, D Nageshwar; Talukdar, Rupjyoti

    2017-12-01

    This paper reports preliminary data of an ongoing study that evaluates the association of systemic inflammatory response (SIRS) with early severe acute pancreatitis (ESAP) and compensatory anti-inflammatory response syndrome (characterized by HLA-DR down-regulation) with infected pancreatic necrosis (IPN). Consecutive patients presenting within 72 h of symptom onset with organ dysfunction and/or local complications were included. Following parameters were recorded: demographics, etiology, SIRS, APACHE II, creatinine, BUN. Circulating IL-8, IL-6, IL-10, TNF-alpha concentrations and expression of HLA-DR and IL-10 by qRT-PCR in PBMCs were measured. Strength of associations of cytokine concentration and HLA-DR/IL-10 expression with outcomes was expressed as Hedges' G and relative risk (95% CI). Twenty-eight patients (10 MSAP; 18 SAP) fulfilled inclusion criteria. Twelve patients had ESAP and eight presented with organ failure. Admission SIRS worsened in eight (28.6%) patients over 48 h. Sixteen (57.1%) patients developed primary IPN. Twenty-one (75%) patients had HLA-DR down-regulation during the first week, which persisted to the second week in 12 (42.9%) patients. IL-8, IL-6, and TNF-α progressively increased from healthy controls to MAP to MSAP to SAP. IL-6 and TNF-α was higher in the patients who developed ESAP (p = 0.01 and 0.05, respectively). Patients who died within the first week also had a significantly elevated concentration of IL-6 and TNF-α (p = 0.02 and 0.01, respectively). The relative risk (95% CI) of developing primary IPN with persistent HLA-DR down-regulation till the second week of illness was 11.3 (1.6-82.4; p = 0.01). Our study objectively demonstrates significant association of ESAP and early mortality with primary cytokine response, and development of IPN with persistent HLA-DR down-regulation.

  19. Effects of Acute Endurance Exercise Performed in the Morning and Evening on Inflammatory Cytokine and Metabolic Hormone Responses.

    Directory of Open Access Journals (Sweden)

    Hyeon-Ki Kim

    Full Text Available To compare the effects of endurance exercise performed in the morning and evening on inflammatory cytokine responses in young men.Fourteen healthy male participants aged 24.3 ± 0.8 years (mean ± standard error performed endurance exercise in the morning (0900-1000 h on one day and then in the evening (1700-1800 h on another day with an interval of at least 1 week between each trial. In both the morning and evening trials, the participants walked for 60 minutes at approximately 60% of the maximal oxygen uptake (VO2max on a treadmill. Blood samples were collected to determine hormones and inflammatory cytokines at pre-exercise, immediately post exercise, and 2 h post exercise.Plasma interleukin (IL-6 and adrenaline concentrations were significantly higher immediately after exercise in the evening trial than in the morning trial (P < 0.01, both. Serum free fatty acids concentrations were significantly higher in the evening trial than in the morning trial at 2 h after exercise (P < 0.05. Furthermore, a significant correlation was observed between the levels of IL-6 immediately post-exercise and free fatty acids 2 h post-exercise in the evening (r = 0.68, P < 0.01.These findings suggest that the effect of acute endurance exercise in the evening enhances the plasma IL-6 and adrenaline concentrations compared to that in the morning. In addition, IL-6 was involved in increasing free fatty acids, suggesting that the evening is more effective for exercise-induced lipolysis compared with the morning.

  20. Astaxanthin alleviated acute lung injury by inhibiting oxidative/nitrative stress and the inflammatory response in mice.

    Science.gov (United States)

    Bi, Jianbin; Cui, Ruixia; Li, Zeyu; Liu, Chang; Zhang, Jingyao

    2017-11-01

    The purpose of the present study was to assess the effect of astaxanthin (ASX) treatment on the acute lung injury (ALI) induced by cecal ligation and puncture (CLP) in mice. Mice were randomly allocated into the following groups: (1) the saline control group, in which mice were given saline before sham operation; (2) the ASX control group, in which mice received ASX before sham operation; (3) the ALI group, in which mice were given saline before CLP operation; and (4) the ALI+ASX group, in which mice received ASX before CLP operation. ASX was dissolved in olive oil and administrated by oral gavage for 14days consecutively before the CLP or sham operation. In experiment 1, Kaplan-Meier survival analysis was conducted for 72h after CLP. In experiment 2, blood, bronchoalveolar lavage fluid (BALF) and lung tissues were collected at 24h after the CLP or sham operation to determine the severity of lung injury. The results showed that ASX treatment could significantly decrease the CLP-induced mortality rate in mice. Meanwhile, ASX treatment significantly attenuated CLP-induced lung histopathological injury, inflammatory infiltration, total protein and albumin concentration, and total cell and neutrophil counts in the BALF. Furthermore, ASX treatment alleviated oxidative/nitrative stress, inflammation levels and pulmonary apoptosis in lung tissues. In addition, ASX treatment markedly down-regulated the expression of inducible nitric oxide synthase (i-NOS), nitrotyrosine (NT) and nuclear factor-kappa B (NF-Κb) P65 in the lung tissues compared with that in the ALI group. Astaxanthin treatment had markedly protective effect against ALI in mice, and the potential mechanism is associated with its ability to inhibit the inflammatory response, oxidative/nitrative stress, and pulmonary apoptosis, as well as down-regulate NF-κB P65 expression. Copyright © 2017. Published by Elsevier Masson SAS.

  1. Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in D-galactose-induced aging rats

    Directory of Open Access Journals (Sweden)

    Liu C

    2017-03-01

    Full Text Available Chao Liu,1,* Jie Hu,1,* Zhi Mao,1,* Hongjun Kang,1 Hui Liu,1 Wanlei Fu,2 Yangfan Lv,2 Feihu Zhou1 1Department of Critical Care Medicine, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 2Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China *These authors contributed equally to this work Background: Recently, the D-galactose (D-gal-induced mimetic aging rat model has been widely used in studies of age-associated diseases, which have shown that chronic D-gal exposure induces premature aging similar to natural aging in rats. With the increasing rate of sepsis in the geriatric population, an easy-access animal model for preclinical studies of elderly sepsis is urgently needed. This study investigates whether a sepsis model that is established in D-gal-induced aging rats can serve as a suitable model for preclinical studies of elderly patients with sepsis.Objective: To investigate the acute kidney injury (AKI and inflammatory response of sepsis following cecal ligation and puncture (CLP in D-gal-induced aging rats.Methods: Twelve-week-old male Sprague Dawley rats were divided into low-dose D-gal (L D-gal, 125 mg/kg/d, high-dose D-gal (H D-gal, 500 mg/kg/d, and control groups. After daily subcutaneous injection of D-gal for 6 weeks, the CLP method was used to establish a sepsis model.Results: The mortality was 73.3%, 40%, and 33.3% in the H D-gal, L D-gal, and control groups, respectively. Blood urea nitrogen, creatinine, plasma neutrophil gelatinase-associated lipocalin, interleukin-6, interleukin-10, and tumor necrosis factor-α were markedly increased in the H D-gal group after establishment of the sepsis model (H D-gal vs control, P<0.05 at 12 h and 24 h post-CLP. The rate of severe AKI (RIFLE-F at 24 h post-CLP was 43% for both the control and L D-gal groups and 80% for the H D-gal group.Conclusion: High-dose-D-gal-induced aging rats are

  2. Inflammatory sequences in acute pulmonary radiation injury

    International Nuclear Information System (INIS)

    Slauson, D.O.; Hahn, F.F.; Benjamin, S.A.; Chiffelle, T.L.; Jones, R.K.

    1976-01-01

    The histopathologic events in the developing acute pulmonary inflammatory reaction to inhaled particles of Yttrium 90 are detailed. In animals that died or were sacrificed during the first year after inhalation exposure, microscopic findings of acute inflammation predominated and included vascular congestion; stasis; focal hemorrhage; edema; various inflammatory cell infiltrates; cytolysis and desquamation of bronchiolar and alveolar epithelium followed by regeneration; vascular injury and repair; and the eventual development of pulmonary fibrosis. Accumulation of alveolar fibrin deposits was an additional characteristic, though not a constant feature of the early stages of radiation pneumonitis. In addition to the direct effects of radiation on pulmonary cell populations, the histopathologic findings were suggestive of diverse activation of various cellular and humoral mediation systems in their pathogenesis. The potential interrelationships of systems responsible for increased vascular permeability, coagulation and fibrinolysis, chemotaxis, and direct cellular injury were discussed and related to the pathogenesis of the microscopic findings characteristic of early pulmonary radiation injury

  3. Acute Immune-Inflammatory Responses to a Single Bout of Aerobic Exercise in Smokers; The Effect of Smoking History and Status

    Science.gov (United States)

    Kastelein, Tegan Emma; Duffield, Rob; Marino, Frank E.

    2015-01-01

    This study examined the acute immune and inflammatory responses to exercise in smokers compared to non-smokers, and further, the effect of smoking history on these immune-inflammatory responses. Fifty-four recreationally active males who were either smokers (SM; n = 27) or non-smokers (NS; n = 27) were allocated into either young (YSM, YNS) or middle-aged groups (MSM, MNS) based on smoking status. Participants were matched for fitness and smoking habits and following familiarization and baseline testing, undertook an exercise protocol that involved 40 min of cycle ergometry at 50% of VO2peak. Venous blood was obtained pre- and post- (0 min, 1, and 4 h) exercise to measure circulating leukocytes and inflammatory markers interleukin (IL)-6, IL-1β, IL-1ra, and monocyte chemoattractant protein-1 (MCP-1). Compared to MNS, MSM showed elevated basal concentrations of MCP-1, which were increased with a longer smoking history (P exercise, YSM demonstrated an amplified IL-6 response from immediately- to 1 h-post compared to YNS. Furthermore, IL-1ra in YSM was elevated above that of YNS across all time points (P exercise leukocyte response was greater in MSM compared to YSM and non-smokers (P exercise-induced inflammatory responses noted in YSM may be indicative tobacco smoke exposure priming circulating leukocytes to amplify inflammatory responses. PMID:26779179

  4. Lycopene rich extract from red guava (Psidium guajava L.) displays anti-inflammatory and antioxidant profile by reducing suggestive hallmarks of acute inflammatory response in mice.

    Science.gov (United States)

    Vasconcelos, Andreanne G; Amorim, Adriany das G N; Dos Santos, Raimunda C; Souza, Jessica Maria T; de Souza, Luan Kelves M; Araújo, Thiago de S L; Nicolau, Lucas Antonio D; de Lima Carvalho, Lucas; de Aquino, Pedro Everson A; da Silva Martins, Conceição; Ropke, Cristina D; Soares, Pedro Marcos G; Kuckelhaus, Selma Aparecida S; Medeiros, Jand-Venes R; Leite, José Roberto de S A

    2017-09-01

    This study investigated the anti-inflammatory activity of the extract (LEG) and purified (LPG) lycopene from guava (Psidium guajava L.), as well as some mechanisms possibly involved in this effect. The anti-inflammatory activity was initially assessed using paw edema induced by Carrageenan, Dextran, Compound 48/80, Histamine and Prostaglandin E2 in Swiss mice. A peritonitis model was used to evaluate neutrophil migration, the activity of myeloperoxidase (MPO) and reduced glutathione (GSH) concentration; while the effect on the expression of iNOS, COX-2 and NF-κB, was assessed by immunohistochemistry analysis. Results showed that oral and intraperitoneal administration of LEG and LPG inhibited inflammation caused by carrageenan. LPG (12.5mg/kg p.o.) significantly inhibited the edema formation induced by different phlogistic agents and immunostaining for iNOS, COX-2 and NF-κB. Leukocytes migration in paw tissue and peritoneal cavity was reduced, as well as MPO concentration, whereas GSH levels increased. Thus, lycopene-rich extract from red guava has beneficial effect on acute inflammation, offering protection against the consequences of oxidative stress by downregulating inflammatory mediators and inhibiting gene expression involved in inflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The role of Vitamin D in immuno-inflammatory responses in Ankylosing Spondylitis patients with and without Acute Anterior Uveitis.

    Science.gov (United States)

    Mitulescu, T C; Stavaru, C; Voinea, L M; Banica, L M; Matache, C; Predeteanu, D

    2016-01-01

    Hypothesis: Abnormal Vitamin D (Vit D) level could have consequences on the immuno-inflammatory processes in Ankylosing Spondylitis (AS). Aim: The purpose of this study was to analyze the role of Vitamin D in the interplay between immune and inflammation effectors in AS associated-Acute Anterior Uveitis (AAU). Methods and Results: 25-hydroxyvitamin D (Vit D), LL-37 peptide, IL-8 and Serum Amyloid A (SAA) were identified and quantified in the serum/ plasma of thirty-four AS patients [eleven AS patients presenting AAU (AAU AS patients) and twenty-three AS patients without AAU (wAAU AS patients)] and eighteen healthy individuals (Control) using enzyme-linked immunosorbent assay. Acute-phase SAA level was significantly higher in AS patients compared to Controls. Contrary with wAAU AS patients, significantly elevated levels of IL-8, and diminished levels of Vit D characterized AAU AS patients. Regarding LL-37, its level decreased concomitantly with the level of Vit D. When AS patients were subgrouped based on AAU presence or on Vit D level, important associations between immuno-inflammatory assessed markers and AS features were noticed. Generally, Vit D levels were associated indirectly with leukocytes/ neutrophils number or with ESR, CRP, and Fibrinogen levels. The levels of SAA and IL-8 associated directly with AAU or with AAU relapses, especially in AS patients with Vit D insufficiency, while SAA associated directly with infection/ inflammatory markers and with disease activity indexes or with the degree of functional limitation. Discussion: Altered levels of Vit D affect the balance between LL-37, IL-8 and SAA, suggesting an association with AAU, an extra-articular manifestation of AS. Abbreviations: Vit D = Vitamin D, AS = Ankylosing Spondylitis, AAU = Acute Anterior Uveitis, AAU AS = AS patients with AAU, wAAU AS = AS patients without AAU, SSZ = Sulphasalazine, Leu = Leukocytes, Neu = Neutrophils.

  6. Valproic acid mitigates the inflammatory response and prevents acute respiratory distress syndrome in a murine model of Escherichia coli pneumonia at the expense of bacterial clearance.

    Science.gov (United States)

    Kasotakis, George; Galvan, Manuel; King, Elizabeth; Sarkar, Beda; Stucchi, Arthur; Mizgerd, Joseph P; Burke, Peter A; Remick, Daniel

    2017-04-01

    Histone deacetylase inhibitors (HDACI) are members of a family of epigenetic modifying agents with broad anti-inflammatory properties. These anti-inflammatory properties may have important therapeutic implications in acute respiratory distress syndrome (ARDS). However, administration of HDACI may create an immunosuppressive environment conducive to bacterial growth. Accordingly, the aim of the current study is to investigate the effect of HDACI valproic acid (VPA) on host inflammatory response and bacterial burden in a murine model of Escherichia coli pneumonia-induced ARDS. ARDS was induced in male C57BL6 mice (n = 24) by endotracheal instillation of 3 × 10 E. coli. VPA (250 mg/kg) was administered 30 minutes after E. coli instillation in the intervention group. Blood samples were collected at 3 and 6 hours, and animals were sacrificed at 6 hours. Bronchoalveolar lavage (BAL) was performed, and tissue specimens were harvested. Cytokine levels were measured in blood and BAL, and so was transalveolar protein transit. Cell counts and colony forming units were quantified in BAL fluid. VPA reduced neutrophil influx into the lungs and local tissue destruction through decreased myeloperoxidase activity. It also ameliorated the pulmonary and systemic inflammatory response. This led to greater bacterial proliferation in the pulmonary parenchyma. Administration of VPA in a clinically relevant bacterial model of murine ARDS mitigates the host inflammatory response, essentially preventing ARDS, but creates an immunosuppressive environment that favors bacterial overgrowth.

  7. Vaginal Heparan Sulfate Linked to Neutrophil Dysfunction in the Acute Inflammatory Response Associated with Experimental Vulvovaginal Candidiasis.

    Science.gov (United States)

    Yano, Junko; Noverr, Mairi C; Fidel, Paul L

    2017-03-14

    worldwide. Despite an acute inflammatory response by neutrophils during infection, the response fails to reduce the organism. Instead, the response is considered a key process underlying the symptoms of vaginitis. Therefore, it is important to determine the mechanism(s) associated with the lack of vaginal neutrophil antifungal activity. The established mouse model of Candida vaginitis was used to uncover the mechanism of neutrophil dysfunction. Results revealed that heparan sulfate present in the vagina of mice susceptible to chronic vaginitis served as a competitive ligand for the receptor (Mac-1) necessary for fungal recognition and neutrophil-mediated killing. This inhibitory function of heparan sulfate, confirmed through several approaches, provides the first evidence to explain the lack of antifungal immune reactivity during vaginal candidiasis. This finding paves the way for design of therapeutic strategies to reduce/eliminate symptomatic vaginal candidiasis and restore quality of life to those affected. Copyright © 2017 Yano et al.

  8. The systemic inflammatory response syndrome.

    Science.gov (United States)

    Robertson, Charles M; Coopersmith, Craig M

    2006-04-01

    The systemic inflammatory response syndrome (SIRS) is the body's response to an infectious or noninfectious insult. Although the definition of SIRS refers to it as an "inflammatory" response, it actually has pro- and anti-inflammatory components. This review outlines the pathophysiology of SIRS and highlights potential targets for future therapeutic intervention in patients with this complex entity.

  9. Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jiao [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Shetty, Sreerama [Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, TX 75708 (United States); Zhang, Ping [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Gao, Rong; Hu, Yuxin [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Wang, Shuxia [Graduate Center for Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Li, Zhenyu [Division of Cardiovascular Medicine, University of Kentucky, Lexington, KY 40536 (United States); Fu, Jian, E-mail: jian.fu@uky.edu [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States)

    2014-06-01

    The presence of endotoxin in blood can lead to acute kidney injury (AKI) and septic shock. Resolvins, the endogenous lipid mediators derived from docosahexaenoic acid, have been reported to exhibit potent anti-inflammatory action. Using a mouse model of lipopolysaccharide (LPS)-induced AKI, we investigated the effects of aspirin-triggered resolvin D1 (AT-RvD1) on inflammatory kidney injury. Administration of AT-RvD1 1 h after LPS challenge protected the mice from kidney injury as indicated by the measurements of blood urea nitrogen, serum creatinine, and morphological alterations associated with tubular damage. The protective effects were evidenced by decreased neutrophil infiltration in the kidney indicating reduction in inflammation. AT-RvD1 treatment restored kidney cell junction protein claudin-4 expression, which was otherwise reduced after LPS challenge. AT-RvD1 treatment inhibited endotoxin-induced NF-κB activation and suppressed LPS-induced ICAM-1 and VCAM-1 expression in the kidney. Moreover, AT-RvD1 treatment markedly decreased LPS-induced IL-6 level in the kidney and blocked IL-6-mediated signaling including STAT3 and ERK phosphorylation. Our findings demonstrate that AT-RvD1 is a potent anti-inflammatory mediator in LPS-induced kidney injury, and AT-RvD1 has therapeutic potential against AKI during endotoxemia.

  10. Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury

    International Nuclear Information System (INIS)

    Chen, Jiao; Shetty, Sreerama; Zhang, Ping; Gao, Rong; Hu, Yuxin; Wang, Shuxia; Li, Zhenyu; Fu, Jian

    2014-01-01

    The presence of endotoxin in blood can lead to acute kidney injury (AKI) and septic shock. Resolvins, the endogenous lipid mediators derived from docosahexaenoic acid, have been reported to exhibit potent anti-inflammatory action. Using a mouse model of lipopolysaccharide (LPS)-induced AKI, we investigated the effects of aspirin-triggered resolvin D1 (AT-RvD1) on inflammatory kidney injury. Administration of AT-RvD1 1 h after LPS challenge protected the mice from kidney injury as indicated by the measurements of blood urea nitrogen, serum creatinine, and morphological alterations associated with tubular damage. The protective effects were evidenced by decreased neutrophil infiltration in the kidney indicating reduction in inflammation. AT-RvD1 treatment restored kidney cell junction protein claudin-4 expression, which was otherwise reduced after LPS challenge. AT-RvD1 treatment inhibited endotoxin-induced NF-κB activation and suppressed LPS-induced ICAM-1 and VCAM-1 expression in the kidney. Moreover, AT-RvD1 treatment markedly decreased LPS-induced IL-6 level in the kidney and blocked IL-6-mediated signaling including STAT3 and ERK phosphorylation. Our findings demonstrate that AT-RvD1 is a potent anti-inflammatory mediator in LPS-induced kidney injury, and AT-RvD1 has therapeutic potential against AKI during endotoxemia

  11. Roles of p38 MAPK in the regulation of the inflammatory response to swine influenza virus-induced acute lung injury in mice.

    Science.gov (United States)

    Wei, D; Huang, Z H; Zhang, R H; Wang, C L; Xu, M J; Liu, B J; Wang, G H; Xu, T

    2014-01-01

    Swine influenza virus (SIV), one of the most important zoonotic agents, is associated with major public health concerns. The current study was conducted to investigate the role of p38 mitogen-activated protein kinase (p38 MAPK) in the regulation of the inflammatory response to acute lung injury (ALI) induced by SIV of H9N2 subtype (H9N2-SIV) in mice. For this purpose, BALB/c mice were intranasally infected with 20 LD(50) of H9N2-SIV (infected group), while non-infected mice served as control (control group). To assess the effect of p38 MAPK, its specific inhibitor SB203580 was employed followed by SIV infection (SB group). At various times after infection, mouse lungs were subjected to pathological and histological observations and detection of inflammatory cytokines tumor necrosis factor α (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 and phosphorylated p38 MAPK. The obtained results showed obvious inflammatory responses, injury and raised levels of inflammatory cytokines and phosphorylated p38 MAPK in the lungs of virus-infected mice. In the mice inoculated with the virus alone, the level of phosphorylated p38 MAPK increased from day 2 and peaked at day 6 post infection (p.i.). However, SB203580 caused lower increases in inflammatory cytokines and phosphorylated p38 MAPK and a milder lung injury. These findings indicate that the activation of p38 MAPK upregulated the inflammatory responses to H9N2-SIV-induced ALI, increased its severity and promoted the production of inflammatory cytokines.

  12. Importance of TLR2 on hepatic immune and non-immune cells to attenuate the strong inflammatory liver response during Trypanosoma cruzi acute infection.

    Directory of Open Access Journals (Sweden)

    Eugenio Antonio Carrera-Silva

    Full Text Available BACKGROUND: Toll-like receptors (TLR and cytokines play a central role in the pathogen clearance as well as in pathological processes. Recently, we reported that TLR2, TLR4 and TLR9 are differentially modulated in injured livers from BALB/c and C57BL/6 (B6 mice during Trypanosoma cruzi infection. However, the molecular and cellular mechanisms involved in local immune response remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we demonstrate that hepatic leukocytes from infected B6 mice produced higher amounts of pro-inflammatory cytokines than BALB/c mice, whereas IL10 and TGFβ were only released by hepatic leukocytes from BALB/c. Strikingly, a higher expression of TLR2 and TLR4 was observed in hepatocytes of infected BALB/c mice. However, in infected B6 mice, the strong pro-inflammatory response was associated with a high and sustained expression of TLR9 and iNOS in leukocytes and hepatic tissue respectively. Additionally, co-expression of gp91- and p47-phox NADPH oxidase subunits were detected in liver tissue of infected B6 mice. Notably, the pre-treatment previous to infection with Pam3CSK4, TLR2-agonist, induced a significant reduction of transaminase activity levels and inflammatory foci number in livers of infected B6 mice. Moreover, lower pro-inflammatory cytokines and increased TGFβ levels were detected in purified hepatic leukocytes from TLR2-agonist pre-treated B6 mice. CONCLUSIONS/SIGNIFICANCE: Our results describe some of the main injurious signals involved in liver immune response during the T. cruzi acute infection. Additionally we show that the administration of Pam3CSk4, previous to infection, can attenuate the exacerbated inflammatory response of livers in B6 mice. These results could be useful to understand and design novel immune strategies in controlling liver pathologies.

  13. Inflammatory response after nailing.

    Science.gov (United States)

    Kanakaris, Nikolaos K; Anthony, Christopher; Papasotiriou, Antonios; Giannoudis, Peter V

    2017-06-01

    Intramedullary nailing, as the gold standard stabilisation method of most long bones, has been tailed by its extensive use as the basic tool of investigating the immune response to trauma in many large and small animal models, as well as at the clinical setting. Over the last few decades a complex map of interactions between pro and anti-inflammatory pathways has been the result of these significant global research efforts. Parallel to the evolution of modern nailing and reaming techniques, significant developments at the fields of other disciplines relevant to trauma care, has improved the contemporary management of injured patients, challenging previous concepts and altering clinical barriers. The current article aims to summarise the current understanding of the effect of instrumenting the medullary canal after trauma, and hint on potential future directions. Copyright © 2017. Published by Elsevier Ltd.

  14. Anti-RAGE antibody selectively blocks acute systemic inflammatory responses to LPS in serum, liver, CSF and striatum.

    Science.gov (United States)

    Gasparotto, Juciano; Ribeiro, Camila Tiefensee; Bortolin, Rafael Calixto; Somensi, Nauana; Fernandes, Henrique Schaan; Teixeira, Alexsander Alves; Guasselli, Marcelo Otavio Rodrigues; Agani, Crepin Aziz Jose O; Souza, Natália Cabral; Grings, Mateus; Leipnitz, Guilhian; Gomes, Henrique Mautone; de Bittencourt Pasquali, Matheus Augusto; Dunkley, Peter R; Dickson, Phillip W; Moreira, José Claudio Fonseca; Gelain, Daniel Pens

    2017-05-01

    Systemic inflammation induces transient or permanent dysfunction in the brain by exposing it to soluble inflammatory mediators. The receptor for advanced glycation endproducts (RAGE) binds to distinct ligands mediating and increasing inflammatory processes. In this study we used an LPS-induced systemic inflammation model in rats to investigate the effect of blocking RAGE in serum, liver, cerebrospinal fluid (CSF) and brain (striatum, prefrontal cortex, ventral tegmental area and substantia nigra). Intraperitoneal injection of RAGE antibody (50μg/kg) was followed after 1h by a single LPS (5mg/kg) intraperitoneal injection. Twenty-four hours later, tissues were isolated for analysis. RAGE antibody reduced LPS-induced inflammatory effects in both serum and liver; the levels of proinflammatory cytokines (TNF-α, IL-1β) were decreased and the phosphorylation/activation of RAGE downstream targets (ERK1/2, IκB and p65) in liver were significantly attenuated. RAGE antibody prevented LPS-induced effects on TNF-α and IL-1β in CSF. In striatum, RAGE antibody inhibited increases in IL-1β, Iba-1, GFAP, phospho-ERK1/2 and phospho-tau (ser202), as well as the decrease in synaptophysin levels. These effects were caused by systemic RAGE inhibition, as RAGE antibody did not cross the blood-brain barrier. RAGE antibody also prevented striatal lipoperoxidation and activation of mitochondrial complex II. In conclusion, blockade of RAGE is able to inhibit inflammatory responses induced by LPS in serum, liver, CSF and brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Mice deficient in interferon-gamma or interferon-gamma receptor 1 have distinct inflammatory responses to acute viral encephalomyelitis.

    Science.gov (United States)

    Lee, Eun-Young; Schultz, Kimberly L W; Griffin, Diane E

    2013-01-01

    Interferon (IFN)-gamma is an important component of the immune response to viral infections that can have a role both in controlling virus replication and inducing inflammatory damage. To determine the role of IFN-gamma in fatal alphavirus encephalitis, we have compared the responses of wild type C57BL/6 (WTB6) mice with mice deficient in either IFN-gamma (GKO) or the alpha-chain of the IFN-gamma receptor (GRKO) after intranasal infection with a neuroadapted strain of sindbis virus. Mortalities of GKO and GRKO mice were similar to WTB6 mice. Both GKO and GRKO mice had delayed virus clearance from the brain and spinal cord, more infiltrating perforin(+) cells and lower levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mRNAs than WTB6 mice. However, inflammation was more intense in GRKO mice than WTB6 or GKO mice with more infiltrating CD3(+) T cells, greater expression of major histocompatibility complex-II and higher levels of interleukin-17A mRNA. Fibroblasts from GRKO embryos did not develop an antiviral response after treatment with IFN-gamma, but showed increases in TNF-alpha, IL-6, CXCL9 and CXCL10 mRNAs although these increases developed more slowly and were less intense than those of WTB6 fibroblasts. These data indicate that both GKO and GRKO mice fail to develop an IFN-gamma-mediated antiviral response, but differ in regulation of the inflammatory response to infection. Therefore, GKO and GRKO cannot be considered equivalent when assessing the role of IFN-gamma in CNS viral infections.

  16. COLIN trial: Value of colchicine in the treatment of patients with acute myocardial infarction and inflammatory response.

    Science.gov (United States)

    Akodad, Mariama; Lattuca, Benoît; Nagot, Nicolas; Georgescu, Vera; Buisson, Mathilde; Cristol, Jean-Paul; Leclercq, Florence; Macia, Jean-Christophe; Gervasoni, Richard; Cung, Thien-Tri; Cade, Stéphane; Cransac, Frédéric; Labour, Jessica; Dupuy, Anne-Marie; Roubille, François

    Inflammation is involved during acute myocardial infarction, and could be an interesting target to prevent ischaemia-reperfusion injuries. Colchicine, known for its pleiotropic anti-inflammatory effects, could decrease systemic inflammation in this context. To evaluate the impact of colchicine on inflammation in patients admitted for ST-segment elevation myocardial infarction (STEMI). All patients admitted for STEMI with one of the main coronary arteries occluded, and successfully treated with percutaneous coronary intervention, were included consecutively. Patients were randomized to receive either 1mg colchicine once daily for 1 month plus optimal medical treatment or optimal medical treatment only. C-reactive protein (CRP) was assessed at admission and daily until hospital discharge. The primary endpoint was CRP peak value during the index hospitalization. Forty-four patients were included: 23 were treated with colchicine; 21 received conventional treatment only. At baseline, both groups were well balanced regarding age, sex, risk factors, thrombolysis in myocardial infarction flow and reperfusion delay. The culprit artery was more often the left anterior descending artery in the colchicine group (P=0.07), reflecting a more severe group. There was no significant difference in mean CRP peak value between the colchicine and control groups (29.03mg/L vs 21.86mg/L, respectively; P=0.36), even after adjustment for type of culprit artery (26.99 vs 24.99mg/L, respectively; P=0.79). In our study, the effect of colchicine on inflammation in the context of STEMI could not be demonstrated. Further larger studies may clarify the impact of colchicine in acute myocardial infarction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Dynamics of Acute Local Inflammatory Response after Autologous Transplantation of Muscle-Derived Cells into the Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Anna Burdzinska

    2014-01-01

    Full Text Available The vast majority of myoblasts transplanted into the skeletal muscle die within the first week after injection. Inflammatory response to the intramuscular cell transfer was studied in allogeneic but not in autologous model. The aim of this study was to evaluate immune reaction to autotransplantation of myogenic cells and to assess its dynamics within the first week after injection. Muscle-derived cells or medium alone was injected into the intact skeletal muscles in autologous model. Tissue samples were collected 1, 3, and 7 days after the procedure. Our analysis revealed the peak increase of the gene expression of all evaluated cytokines (Il-1α, Il-1β, Il-6, Tgf-β, and Tnf-α at day 1. The mRNA level of analyzed cytokines normalized in subsequent time points. The increase of Il-β gene expression was further confirmed at the protein level. Analysis of the tissue sections revealed rapid infiltration of injected cell clusters with neutrophils and macrophages. The inflammatory infiltration was almost completely resolved at day 7. The survived cells were able to participate in the muscle regeneration process. Presented results demonstrate that autotransplanted muscle-derived cells induce classical early immune reaction in the site of injection which may contribute to cellular graft elimination.

  18. Effects of Acute Endurance Exercise Performed in the Morning and Evening on Inflammatory Cytokine and Metabolic Hormone Responses.

    Science.gov (United States)

    Kim, Hyeon-Ki; Konishi, Masayuki; Takahashi, Masaki; Tabata, Hiroki; Endo, Naoya; Numao, Shigeharu; Lee, Sun-Kyoung; Kim, Young-Hak; Suzuki, Katsuhiko; Sakamoto, Shizuo

    2015-01-01

    To compare the effects of endurance exercise performed in the morning and evening on inflammatory cytokine responses in young men. Fourteen healthy male participants aged 24.3 ± 0.8 years (mean ± standard error) performed endurance exercise in the morning (0900-1000 h) on one day and then in the evening (1700-1800 h) on another day with an interval of at least 1 week between each trial. In both the morning and evening trials, the participants walked for 60 minutes at approximately 60% of the maximal oxygen uptake (VO2max) on a treadmill. Blood samples were collected to determine hormones and inflammatory cytokines at pre-exercise, immediately post exercise, and 2 h post exercise. Plasma interleukin (IL)-6 and adrenaline concentrations were significantly higher immediately after exercise in the evening trial than in the morning trial (P morning trial at 2 h after exercise (P morning. In addition, IL-6 was involved in increasing free fatty acids, suggesting that the evening is more effective for exercise-induced lipolysis compared with the morning.

  19. Systemic inflammatory responses in asthma

    NARCIS (Netherlands)

    Hove, W. ten

    2007-01-01

    In asthma, inflammatory cells undergo a process referred to as priming. During priming responses, cells are not directly activated by inflammatory stimuli, but acquire increased responsiveness towards heterologous stimuli. The focus of the studies presented in the thesis of Willem ten Hove was

  20. Imbalanced immune responses involving inflammatory molecules and immune-related pathways in the lung of acute and subchronic arsenic-exposed mice.

    Science.gov (United States)

    Li, Jinlong; Zhao, Lu; Zhang, Yang; Li, Wei; Duan, Xiaoxu; Chen, Jinli; Guo, Yuanyuan; Yang, Shan; Sun, Guifan; Li, Bing

    2017-11-01

    treatment. Conclusively, our present study demonstrated both acute and subchronic oral administration of arsenic triggers multiple pulmonary immune responses involving inflammatory molecules and T-cell differentiation, which might be closely associated with the imbalanced redox status and activation of immune-related MAPKs, NF-κB and anti-inflammatory NRF2 pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Inflammatory Biomarkers During Bacterial Acute Rhinosinusitis.

    Science.gov (United States)

    Autio, Timo J; Koskenkorva, Timo; Koivunen, Petri; Alho, Olli-Pekka

    2018-02-21

    Diagnosis of bacterial acute rhinosinusitis is difficult. Several attempts have been made to clarify the diagnostic criteria. Inflammatory biomarkers are easily obtainable variables that could shed light on both the pathophysiology and diagnosis of bacterial acute rhinosinusitis. The purpose of this review article is to assess literature concerning the course of inflammatory biomarkers during acute rhinosinusitis and the use of inflammatory biomarkers in diagnosing bacterial acute rhinosinusitis. We included C-reactive protein, erythrocyte sedimentation rate, white blood cell counts, procalcitonin, and nasal nitric oxide in this review and found that especially elevated C-reactive protein and erythrocyte sedimentation rate are related to a higher probability of a bacterial cause of acute rhinosinusitis. Still, normal levels of these two biomarkers are quite common as well, or the levels can be heightened even during viral respiratory infection without suspicion of bacterial involvement. Elevated levels of C-reactive protein or erythrocyte sedimentation rate support diagnosis of bacterial acute rhinosinusitis, but due to a lack of sensitivity, they should not be used to screen patients for bacterial acute rhinosinusitis.

  2. Seasonal trend of acute pelvic inflammatory disease.

    Science.gov (United States)

    Xholli, Anjeza; Cannoletta, Marianna; Cagnacci, Angelo

    2014-05-01

    Many infections follow a seasonal trend. Aim of our study was to check whether acute pelvic inflammatory disease (PID) follows a seasonal progress. In a retrospective study on 12,152 hospital records, 158 cases of acute pelvic inflammatory disease were identified. Periodogram analysis was applied to the date of pelvic inflammatory disease admission and to related environmental factors, such as temperature and photoperiod. Pelvic inflammatory disease follows a seasonal rhythm with mean to peak variation of 23 % and maximal values in September (±37.2 days). The rhythm, more evident in married women, is related to the rhythm of temperature advanced by 2 months and of photoperiod advanced by 3 months. Cases of pelvic inflammatory disease are more frequent than expected in unmarried (36 vs. 17.3/34,626, p = 0.015), particularly divorced women 30-40 years of age. Our study evidences a seasonal trend and confirms unmarried, particularly divorced status, as important risk factor for acute pelvic inflammatory disease.

  3. The Systemic Pro-Inflammatory Response in Sepsis

    NARCIS (Netherlands)

    de Jong, Hanna Katrien; van der Poll, Tom; Wiersinga, Willem Joost

    2010-01-01

    The systemic inflammatory response syndrome (SIRS) is the predominantly cytokine-mediated, pro-inflammatory response of the host to invading pathogens and is considered the hallmark sign of sepsis. Molecular components of this response can be divided into cytokines, plasma cascades and acute phase

  4. Effects of melatonin on the acute inflammatory response associated with endoscopic retrograde cholangiopancreatography: A randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Hernández-Velázquez, B; Camara-Lemarroy, C R; González-González, J A; García-Compean, D; Monreal-Robles, R; Cordero-Pérez, P; Muñoz-Espinosa, L E

    2016-01-01

    Endoscopic retrograde cholangiopancreatography (ERCP) is associated with an acute inflammatory response and melatonin has a variety of immunomodulatory and antioxidant effects studied experimentally in pancreatobiliary pathology. The aim of our study was to evaluate the effects of peri-procedural administration of melatonin on the inflammatory response and lipid peroxidation associated with ERCP. In this proof-of-concept clinical trial, 37 patients with a high probability of choledocholithiasis were randomized to receive peri-procedure (ERCP) melatonin or placebo. We measured the serum concentration of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), lipid peroxidation, amylase, and liver function tests 24h before and after the procedure. We found no pre-procedure or post-procedure differences between the melatonin group or the placebo group (P>.05) in the serum concentrations of TNF-alpha (melatonin: 153.8 vs. 149.4ng/m; placebo: 103.5 vs. 107.3ng/ml), IL-6 (melatonin: 131.8 vs. 133.3ng/ml; placebo: 177.8 vs. 197.8ng/ml), or VEGF (melatonin: 157.3 vs. 157.8pg/ml; placebo: 97.3 vs. 97.8pg/ml), or in relation to lipid peroxidation (melatonin: 39.2 vs. 72.3μg/ml; placebo: 66.4 vs. 90.5μg/ml). After ERCP, a significant decrease in the AST, ALT, and total bilirubin levels was found only in the melatonin group (P<.05). The administration of melatonin was safe and tolerable. Melatonin is safe and tolerable in patients undergoing ERCP, but it does not appear to affect inflammatory cytokine concentrations or lipid peroxidation. Copyright © 2016 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  5. Low-methoxyl lemon pectin attenuates inflammatory responses and improves intestinal barrier integrity in caerulein-induced experimental acute pancreatitis

    NARCIS (Netherlands)

    Sun, Yajun; He, Yue; Wang, Fei; Zhang, Hao; de Vos, Paul; Sun, Jia

    Scope: Acute pancreatitis (AP) is a common clinical acute abdominal disease. The intestinal injury associated with AP will aggravate the condition retroactively. This study investigates whether the low-methoxyl pectin (LMP) isolated from lemon could attenuate AP and associated intestinal injury.

  6. Voluntary Wheel Running Reduces the Acute Inflammatory Response to Liver Carcinogen in a Sex-specific Manner

    DEFF Research Database (Denmark)

    Bay, M L; Gehl, Julie; Pedersen, Bente Klarlund

    2017-01-01

    and hepatic acute inflammation, which was associated with a higher baseline expression of the detoxifying enzyme glutathione S-transferase and lower expression of ERα in male mice. Voluntary wheel running attenuated systemic and hepatic inflammation, in particular in the female mice, and shifted the peak time...

  7. Inflammatory Response During Myocardial Infarction.

    Science.gov (United States)

    Oliveira, Joaquim B; Soares, Alexandre A S M; Sposito, Andrei C

    2018-01-01

    The occlusion of a coronary artery by a thrombus generated on a ruptured atherosclerotic plaque has been pursued in the last decades as a determining event for the clinical outcome after myocardial infarction (MI). Yet, MI causes a cell death wave front, which triggers an inflammatory response to clear cellular debris, and which in excess can double the myocardial lesion and influence the clinical prognosis in the short and long term. Accordingly, proper, timely regulated inflammatory response has now been considered a second pivotal player in cardiac recovery after MI justifying the search for pharmacological strategies to modulate inflammatory effectors. This chapter reviews the key events and the main effectors of inflammation after myocardial ischemic insult, as well as the contribution of this phenomenon to the progression of atherosclerosis. © 2018 Elsevier Inc. All rights reserved.

  8. Gene expression profiling in brain of mice exposed to the marine neurotoxin ciguatoxin reveals an acute anti-inflammatory, neuroprotective response.

    Science.gov (United States)

    Ryan, James C; Morey, Jeanine S; Bottein, Marie-Yasmine Dechraoui; Ramsdell, John S; Van Dolah, Frances M

    2010-08-26

    Ciguatoxins (CTXs) are polyether marine neurotoxins and potent activators of voltage-gated sodium channels. This toxin is carried by multiple reef-fish species and human consumption of ciguatoxins can result in an explosive gastrointestinal/neurologic illness. This study characterizes the global transcriptional response in mouse brain to a symptomatic dose of the highly toxic Pacific ciguatoxin P-CTX-1 and additionally compares this data to transcriptional profiles from liver and whole blood examined previously. Adult male C57/BL6 mice were injected with 0.26 ng/g P-CTX-1 while controls received only vehicle. Animals were sacrificed at 1, 4 and 24 hrs and transcriptional profiling was performed on brain RNA with Agilent whole genome microarrays. RT-PCR was used to independently validate gene expression and the web tool DAVID was used to analyze gene ontology (GO) and molecular pathway enrichment of the gene expression data. A pronounced 4°C hypothermic response was recorded in these mice, reaching a minimum at 1 hr and lasting for 8 hrs post toxin exposure. Ratio expression data were filtered by intensity, fold change and p-value, with the resulting data used for time course analysis, K-means clustering, ontology classification and KEGG pathway enrichment. Top GO hits for this gene set included acute phase response and mono-oxygenase activity. Molecular pathway analysis showed enrichment for complement/coagulation cascades and metabolism of xenobiotics. Many immediate early genes such as Fos, Jun and Early Growth Response isoforms were down-regulated although others associated with stress such as glucocorticoid responsive genes were up-regulated. Real time PCR confirmation was performed on 22 differentially expressed genes with a correlation of 0.9 (Spearman's Rho, p < 0.0001) with microarray results. Many of the genes differentially expressed in this study, in parallel with the hypothermia, figure prominently in protection against neuroinflammation. Pathologic

  9. Gene expression profiling in brain of mice exposed to the marine neurotoxin ciguatoxin reveals an acute anti-inflammatory, neuroprotective response

    Directory of Open Access Journals (Sweden)

    Ryan James C

    2010-08-01

    Full Text Available Abstract Background Ciguatoxins (CTXs are polyether marine neurotoxins and potent activators of voltage-gated sodium channels. This toxin is carried by multiple reef-fish species and human consumption of ciguatoxins can result in an explosive gastrointestinal/neurologic illness. This study characterizes the global transcriptional response in mouse brain to a symptomatic dose of the highly toxic Pacific ciguatoxin P-CTX-1 and additionally compares this data to transcriptional profiles from liver and whole blood examined previously. Adult male C57/BL6 mice were injected with 0.26 ng/g P-CTX-1 while controls received only vehicle. Animals were sacrificed at 1, 4 and 24 hrs and transcriptional profiling was performed on brain RNA with Agilent whole genome microarrays. RT-PCR was used to independently validate gene expression and the web tool DAVID was used to analyze gene ontology (GO and molecular pathway enrichment of the gene expression data. Results A pronounced 4°C hypothermic response was recorded in these mice, reaching a minimum at 1 hr and lasting for 8 hrs post toxin exposure. Ratio expression data were filtered by intensity, fold change and p-value, with the resulting data used for time course analysis, K-means clustering, ontology classification and KEGG pathway enrichment. Top GO hits for this gene set included acute phase response and mono-oxygenase activity. Molecular pathway analysis showed enrichment for complement/coagulation cascades and metabolism of xenobiotics. Many immediate early genes such as Fos, Jun and Early Growth Response isoforms were down-regulated although others associated with stress such as glucocorticoid responsive genes were up-regulated. Real time PCR confirmation was performed on 22 differentially expressed genes with a correlation of 0.9 (Spearman's Rho, p Conclusions Many of the genes differentially expressed in this study, in parallel with the hypothermia, figure prominently in protection against

  10. A quantitative immunohistochemical study on the time-dependent course of acute inflammatory cellular response to human brain injury.

    Science.gov (United States)

    Hausmann, R; Kaiser, A; Lang, C; Bohnert, M; Betz, P

    1999-01-01

    The time-dependent inflammatory cell reaction in human cortical contusions has been investigated during the first 30 weeks after blunt head injury. Immunohistochemical staining was carried out using CD 15 for granulocytes and LCA, CD 3 and UCHL-1 for mononuclear leucocytes. In order to provide reliable data for a forensic wound age estimation, the intensity of the cellular reaction was evaluated with a quantitative image analysis system. CD 15-labelled granulocytes were detectable earliest 10 min after brain injury, whereas significantly increased numbers of mononuclear leucocytes occurred in cortical contusions after a postinfliction interval of at least 1.1 days (LCA), 2 days (CD 3) or 3.7 days (UCHL-1), respectively.

  11. Agmatine Protects against Zymosan-Induced Acute Lung Injury in Mice by Inhibiting NF-κB-Mediated Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Xuanfei Li

    2014-01-01

    Full Text Available Acute lung injury (ALI is characterized by overwhelming lung inflammation and anti-inflammation treatment is proposed to be a therapeutic strategy for ALI. Agmatine, a cationic polyamine formed by decarboxylation of L-arginine, is an endogenous neuromodulator that plays protective roles in diverse central nervous system (CNS disorders. Consistent with its neuromodulatory and neuroprotective properties, agmatine has been reported to have beneficial effects on depression, anxiety, hypoxic ischemia, Parkinson’s disease, and gastric disorder. In this study, we tested the effect of agmatine on the lung inflammation induced by Zymosan (ZYM challenge in mice. We found that agmatine treatment relieved ZYM-induced acute lung injury, as evidenced by the reduced histological scores, wet/dry weight ratio, and myeloperoxidase activity in the lung tissue. This was accompanied by reduced levels of TNF-α, IL-1β, and IL-6 in lung and bronchoalveolar lavage fluid and decreased iNOS expression in lung. Furthermore, agmatine inhibited the phosphorylation and degradation of IκB and subsequently blocked the activation of nuclear factor (NF-κB induced by Zymosan. Taken together, our results showed that agmatine treatment inhibited NF-κB signaling in lungs and protected mice against ALI induced by Zymosan, suggesting agmatine may be a potential safe and effective approach for the treatment of ALI.

  12. Use of serum amyloid A and other acute phase reactants to monitor the inflammatory response after castration in horses: a field study.

    Science.gov (United States)

    Jacobsen, S; Jensen, J C; Frei, S; Jensen, A L; Thoefner, M B

    2005-11-01

    Early recognition of excessive inflammation and infectious complications after surgery, leading to early institution of therapy, reduces post operative discomfort and facilitates recovery. Because serum amyloid A (SAA) is a highly sensitive marker of inflammation, measurements of SAA and other acute phase reactants in the equine surgical patient may be valuable in assisting clinical assessment of post operative inflammation. To investigate changes in inflammatory markers after castration and to correlate levels of acute phase reactants with clinical severity of inflammation after castration. Leucocyte numbers and blood levels of iron, SAA and fibrinogen were determined before castration and on Days 3 and 8 post operatively in 2 groups of horses; Group 1 (n = 11) had mild post operative inflammation and an uncomplicated recovery and Group 2 (n = 7) had local clinical signs of moderate to severe inflammation. Both groups had elevated serum SAA levels at Day 3 post operatively. In Group 1 concentrations had returned to preoperative levels by Day 8, whereas in Group 2 concentrations remained elevated. Plasma fibrinogen concentrations in serum increased to equal levels in both groups and stayed elevated throughout the study period. Serum iron concentrations of Group 1 did not change in response to castration, whereas concentrations in Group 2 decreased below preoperative levels on Day 8. Leucocyte numbers remained unchanged during the post operative period in both groups. Serum SAA and iron profiles reflected the course of inflammation and their levels correlated with the clinical severity of inflammation. In contrast, fever and changes in leucocyte numbers, which are usually considered to be hallmarks of inflammation and infection, were not useful for monitoring post operative recovery. Measurements of SAA and iron may improve post operative monitoring. As sustained inflammation may indicate that the surgical wound has become infected, SAA and iron measurements may

  13. Fish Oil-Based Fat Emulsion Reduces Acute Kidney Injury and Inflammatory Response in Antibiotic-Treated Polymicrobial Septic Mice

    Directory of Open Access Journals (Sweden)

    Juey-Ming Shih

    2016-03-01

    Full Text Available Acute kidney injury (AKI is a common complication in sepsis. This study compared the effects of a fish oil-based with a mixed oil fat emulsion on remote renal injury in an antibiotic-treated septic murine model. Mice were randomly assigned to a normal control (NC group and three septic groups. Sepsis was induced by cecal ligation and puncture (CLP. The antibiotic was injected intraperitoneally (IP after CLP and then daily till the time of sacrifice. Three hours after antibiotic treatment, one of the septic groups was injected IP with a fish oil-based emulsion (FO, while the other two groups were given either a mixed oil emulsion (MO or saline (SC. The septic groups were further divided into two separate time groups, with blood and kidneys samples collected at 24 h or 72 h post-CLP. The results showed that sepsis leads to the activation of neutrophils, T helper (Th1/Th-2/Th-17 and Treg cells (p < 0.05. Plasma NGAL and mRNA expressions of renal MyD88 and TLR4 were also enhanced (p < 0.05. Compared to the SC group, the group given the fish oil-based emulsion had decreased plasma NGAL by 22% and Treg by 33%. Furthermore, renal gene expressions of MyD88 and TLR4 reduced by 46% and 62%, respectively, whereas heat shock protein 70 and peroxisome proliferator-activated receptor-γ increased by 158% and 69%, respectively (p < 0.05, at Day 3 after CLP. These results suggest that administration of a fish oil-based emulsion has favorable effects, maintaining blood T cell percentage, downregulating Treg expression, attenuating systemic and local inflammation and offering renal protection under conditions of antibiotic-treated polymicrobial sepsis.

  14. Inflammatory Response in Islet Transplantation

    Directory of Open Access Journals (Sweden)

    Mazhar A. Kanak

    2014-01-01

    Full Text Available Islet cell transplantation is a promising beta cell replacement therapy for patients with brittle type 1 diabetes as well as refractory chronic pancreatitis. Despite the vast advancements made in this field, challenges still remain in achieving high frequency and long-term successful transplant outcomes. Here we review recent advances in understanding the role of inflammation in islet transplantation and development of strategies to prevent damage to islets from inflammation. The inflammatory response associated with islets has been recognized as the primary cause of early damage to islets and graft loss after transplantation. Details on cell signaling pathways in islets triggered by cytokines and harmful inflammatory events during pancreas procurement, pancreas preservation, islet isolation, and islet infusion are presented. Robust control of pre- and peritransplant islet inflammation could improve posttransplant islet survival and in turn enhance the benefits of islet cell transplantation for patients who are insulin dependent. We discuss several potent anti-inflammatory strategies that show promise for improving islet engraftment. Further understanding of molecular mechanisms involved in the inflammatory response will provide the basis for developing potent therapeutic strategies for enhancing the quality and success of islet transplantation.

  15. Compensatory anti-inflammatory response syndrome.

    Science.gov (United States)

    Adib-Conquy, Minou; Cavaillon, Jean-Marc

    2009-01-01

    The concept of 'Compensatory anti-inflammatory response syndrome' (CARS) was proposed in 1997 by Roger Bone (1941-1997) to qualify the consequences of the counter-regulatory mechanisms initiated to limit the overzealous inflammatory process in patients with infectious (sepsis) or non-infectious systemic inflammatory response syndrome (SIRS). One major consequence of CARS is the modification of the immune status that could favour the enhanced susceptibility of intensive care patients to nosocomial infections. Indeed, most animal 'two-hit' models illustrate an enhanced sensitivity to infection after a first insult. However, this observation is highly dependent on the experimental procedure. Numerous functions of circulating leukocytes are altered in sepsis and SIRS patients, as well as in animal models of sepsis or SIRS. However, this is rather a reprogramming of circulating leukocytes, since there is not a global defect of the immune cells functions. Furthermore, within tissues, leukocytes are rather primed or activated than immunosuppressed. Thus, CARS may be considered as an adapted compartmentalized response with the aim to silence some acute proinflammatory genes, and to maintain the possible expression of certain genes involved in the anti-infectious process.

  16. Transvaginal sonography of acute pelvic inflammatory disease

    International Nuclear Information System (INIS)

    Choi, Jin Soo; Kim, Young Hwa; Shin, Hyung Chul; Han, Gun Soo; Kim, Il Young

    1999-01-01

    To determine the value of transvaginal sonography in evaluating women with acute pelvic inflammatory disease (PID). Transvaginal sonography was performed in 25 patients with clinically suggested PID during recent 36 months. The sonographic findings of fallopian tubes and ovaries were analyzed and correlated with pathological findings of 2 fallopian tubes and 19 ovaries in 16 patients who had operations. The correct diagnosis of acute PID was made in 20/25 (80%) by transvaginal sonography. the abnormal sonographic findings of the fallopian tube include tubal thickening or dilatation with internal echo. The sensitivity, specificity, and accuracy for tubal abnormality were 88%, 96%, and 86% , respectively. Ovarian changes were seen on TVS in 14/19 (73%), which include multiple follicular enlargement in 5, tubo-ovarian complex in 9 (tubo-ovarian adhesion in 3, tubo-ovarian abscess in 6). At surgery, the ovay was not involved in all three women who showed tubo-ovarian adhesion on TVS. Among 6 women who showed tubo-ovarian abscess on TVS, tubo-ovarian abscess was confirmed in 3 and the remaining 3 had ovarian cysts. Trandvaginal sonography, a facilitative and accurate modality, is highly sensitive in detecting the abnormality of the tube and useful in differentiating the tubo-ovarian complex in patients with acute PID.

  17. CT findings of acute pelvic inflammatory disease.

    Science.gov (United States)

    Lee, Mi Hee; Moon, Min Hoan; Sung, Chang Kyu; Woo, Hyunsik; Oh, Sohee

    2014-12-01

    To determine the computed tomographic (CT) findings of acute pelvic inflammatory disease (PID). This retrospective, single-institution case-control study was approved by our institutional review board, and the informed consent was waived owing to the retrospective nature of the study. CT images of 32 women with clinically proven acute PID and 32 control subjects with other conditions of similar presentation were retrospectively reviewed. Analysis of CT findings included hepatic capsular enhancement, pelvic fat haziness, complicated ascites, uterine serosal enhancement, tubal thickening, endometritis, and oophoritis. Comparison of CT findings was performed with the Chi square test or the Fisher exact test and logistic regression analysis was used to determine significant CT findings in predicting PID. The CT findings that showed a statistically significant difference were hepatic capsular enhancement on late arterial phase (p = 0.003), pelvic fat haziness (p = 0.045), and tubal thickening (p = 0.001). Subsequent multivariate logistic regression analysis revealed that the presence of hepatic capsular enhancement on late arterial phase and tubal thickening were significant predictors of PID (hepatic capsular enhancement on late arterial phase, p = 0.015, odds ratio [OR] = 4.8; tubal thickening, p = 0.005, OR = 10.5). Diagnostic morphological CT findings in women with clinically proven PID and acute abdominal pain include hepatic capsular enhancement on late arterial phase and tubal thickening.

  18. Pulmonary response to surface‐coated nanotitanium dioxide particles includes induction of acute phase response genes, inflammatory cascades, and changes in microRNAs: A toxicogenomic study

    DEFF Research Database (Denmark)

    Halappanavar, Sabina; Jackson, Petra; Williams, Andrew

    2011-01-01

    in increased levels of mRNA for acute phase markers serum amyloid A‐1 (Saa1) and serum amyloid A‐3 (Saa3), several C‐X‐C and C‐C motif chemokines, and cytokine tumor necrosis factor genes. Protein analysis of Saa1 and 3 showed selective upregulation of Saa3 in lung tissues. Sixteen miRNAs were induced by more...... on pulmonary global messenger RNA (mRNA) and microRNA (miRNA) expression in mouse were characterized to provide insight into the molecular response. Female C57BL/6BomTac mice were exposed for 1 hr daily to 42.4 ± 2.9 (SEM) mg surface‐coated nanoTiO2/m3 for 11 consecutive days by inhalation and were sacrificed...... than 1.2‐fold (adjusted P‐value miR‐1, miR‐449a and revealed dramatic induction of miR‐135b (60‐fold). Thus, inhalation of surface‐coated nanoTiO2 results in changes in the expression of genes associated...

  19. Casticin, an active compound isolated from Vitex Fructus, ameliorates the cigarette smoke-induced acute lung inflammatory response in a murine model.

    Science.gov (United States)

    Lee, Hyeonhoon; Jung, Kyung-Hwa; Lee, Hangyul; Park, Soojin; Choi, Woosung; Bae, Hyunsu

    2015-10-01

    The aim of this study was to determine of the effect of casticin, as an anti-inflammatory agent, on an acute lung inflammation in vivo model established through exposure to cigarette smoke (CS). Casticin is a phytochemical from Vitex species such as Vitex rotundifolia and Vitex agnus-castus that was recently shown to exert an anti-inflammatory effect in vivo. To demonstrate the effects of casticin, C57BL/6 mice were whole-body exposed to mainstream CS or fresh air for two weeks and treated with 1, 2, and 10mg/kg casticin via an i.p. injection. Immune cell infiltrations and cytokine productions were assessed from bronchoalveolar lavage Fluid (BALF), and lung histological analysis was performed. Treatment with casticin was observed to significantly inhibit the numbers of total cells, neutrophils, macrophages, and lymphocytes and reduce the levels of proinflammatory cytokines and chemokines in the BALF. In addition, casticin significantly decreased the infiltration of peribronchial and perivascular inflammatory cells and the epithelium thickness. The results of this study indicate that casticin has significant effects on the lung inflammation induced by CS in a mouse model. According to these outcomes, casticin may have therapeutic potential in inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD). Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Longitudinal analysis of inflammatory biomarkers during acute rhinosinusitis.

    Science.gov (United States)

    Autio, Timo J; Koskenkorva, Timo; Leino, Tuomo K; Koivunen, Petri; Alho, Olli-Pekka

    2017-02-01

    To illuminate the pathophysiology of acute rhinosinusitis (ARS) with sequential monitoring of inflammatory biomarkers during an ARS episode and to clarify their diagnostic usability in bacterial ARS. Inception cohort study with 50 conscripts with ARS. We collected peripheral blood high-sensitive C-reactive protein (hs-CRP), white blood cell (WBC), procalcitonin, and nasal nitric oxide (nNO) counts at 2 to 3 and 9 to 10 days of symptoms during an ARS episode. We simultaneously gathered various clinical parameters and microbiological samples. Bacterial ARS was confirmed with a positive culture of sinus aspirate. Reciprocal correlations and a significant change in biomarker levels between the two visits suggest that ARS involves a local and systemic inflammatory response that was strongest at 2 to 3 days. High-sensitive CRP and nNO reflected responses best (52% had increased CRP levels at 2-3 days; 66% had decreased nNO levels). White blood cell and procalcitonin counts rarely exceeded the reference range. Increased local and systemic inflammatory response were linked to multiple, adenoviral, or influenza A viral etiology or the detection of bacterial ARS. Local response correlated with imaging findings of wide paranasal sinus involvement and ostiomeatal complex occlusion. At 9 to 10 days, elevated (≥ 11 mg/L) and moderately elevated (≥ 49 mg/L) hs-CRP predicted bacterial ARS well (likelihood ratio [LR]+ 3.3 and LR+ 15.8, respectively), but the sensitivity for both findings remained low. Acute rhinosinusitis (particularly bacterial ARS) involves a local and systemic inflammatory response that is strongest at the beginning of symptoms. Elevated hs-CRP supports the diagnosis of bacterial ARS. 4. Laryngoscope, 2016 127:E55-E61, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  1. Expression of acute phase proteins and inflammatory cytokines in mouse mammary gland following Staphylococcus aureus challenge and in response to milk accumulation

    DEFF Research Database (Denmark)

    Nazemi, Sasan; Aalbæk, Bent; Kjelgaard-Hansen, Mads

    2014-01-01

    We used a mouse model of pathogenic (Staphylococcus aureus) and non-pathogenic (teat sealing) mammary inflammation to investigate mRNA expression of several inflammatory cytokines and acute phase proteins (APP) in mammary tissue and liver, and the appearance of some of these factors in plasma...... or lesser extent, whilst expression of APP was up-regulated to a much greater extent. The first appearance of increased cytokine and APP concentrations in plasma and of milk amyloid A (MAA) in milk occurred in advance of the measurable up-regulation of expression, hence their origin cannot be stated...

  2. [Inflammatory biomarkers in ischemic acute coronary syndrome].

    Science.gov (United States)

    Domínguez-Rodríguez, Alberto; Abreu-González, Pedro

    2015-10-01

    Diagnosing acute coronary syndrome (ACS) in the emergency department is often a complex process. Inflammatory markers might be useful for the rapid assessment of a patient's overall risk and might also help predict future episodes. The clinical use of these biomarkers could potentially lower the number of emergency visits and help in the prevention of future adverse events. The aim of this review was to evaluate the clinical utility of markers of cardiovascular inflammation in emergency patients with ACS. Based on a critical analysis of a selection of the literature, we concluded that none of the biomarkers of cardiovascular inflammation would at present be useful for stratifying risk in emergency situations, aiding prognosis, or guiding therapy for patients with ACS.

  3. Marrubium vulgare L. methanolic extract inhibits inflammatory response and prevents cardiomyocyte fibrosis in isoproterenol-induced acute myocardial infarction in rats.

    Science.gov (United States)

    Yousefi, Keyvan; Fathiazad, Fatemeh; Soraya, Hamid; Rameshrad, Maryam; Maleki-Dizaji, Nasrin; Garjani, Alireza

    2014-01-01

    Nowadays, finding new therapeutic compounds from natural products for treatment and prevention of a variety of diseases including cardiovascular disorders is getting a great deal of attention. This approach would result in finding new drugs which are more effective and have fewer side effects than the conventional medicines. The present study was designed to investigate the anti-inflammatory effect of the methanolic extract of Marrubiumvulgare, a popular traditional medicinal herb, on isoproterenol-induced myocardial infarction (MI) in rat model. Male Wistar rats were assigned to 6 groups of control, sham, isoproterenol, and treatment with 10, 20, and 40 mg/kg/12h of the extract given orally concurrent with MI induction. A subcutaneous injection of isoproterenol (100 mg/kg/day) for two consecutive days was used to induce MI. Then, histopathological changes and inflammatory markers were evaluated. Isoproterenol injection increased inflammatory response, as shown by a significant increase in peripheral neutrophil count, myocardial myeloperoxidase (MPO) activity and serum levels of creatinine kinase-MB (CK-MB) and TNF-α (pvulgare extract serum CK-MB was subsided by 55.4%, 52.2% and 69%, respectively. Also treatment with the extract (40 mg/kg) significantly reduced (pvulgare extract has strong protective effects against isoproterenol-induced myocardial infarction and it seems possible that this protection is due to its anti-inflammatory effects.

  4. Ginkgo biloba extracts attenuate lipopolysaccharide-induced inflammatory responses in acute lung injury by inhibiting the COX-2 and NF-κB pathways.

    Science.gov (United States)

    Yao, Xin; Chen, Nan; Ma, Chun-Hua; Tao, Jing; Bao, Jian-An; Zong-Qi, Cheng; Chen, Zu-Tao; Miao, Li-Yan

    2015-01-01

    In the present study, we analyzed the role of Ginkgo biloba extract in lipopolysaccharide(LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS. G. biloba extract (12 and 24 mg·kg(-1)) and dexamethasone (2 mg·kg(-1)), as a positive control, were given by i.p. injection. The cells in the bronchoalveolar lavage fluid (BALF) were counted. The degree of animal lung edema was evaluated by measuring the wet/dry weight ratio. The superoxidase dismutase (SOD) and myeloperoxidase (MPO) activities were assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-a, interleukin-1b, and interleukin-6, were assayed by enzyme-linked immunosorbent assay. Pathological changes of lung tissues were observed by H&E staining. The levels of NF-κB p65 and COX-2 expression were detected by Western blotting. Compared to the LPS group, the treatment with the G. biloba extract at 12 and 24 mg·kg(-1) markedly attenuated the inflammatory cell numbers in the BALF, decreased NF-κB p65 and COX-2 expression, and improved SOD activity, and inhibited MPO activity. The histological changes of the lungs were also significantly improved. The results indicated that G. biloba extract has a protective effect on LPS-induced acute lung injury in mice. The protective mechanism of G. biloba extract may be partly attributed to the inhibition of NF-κB p65 and COX-2 activation. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  5. Ethanol Extract of Antrodia camphorata Grown on Germinated Brown Rice Suppresses Inflammatory Responses in Mice with Acute DSS-Induced Colitis

    Directory of Open Access Journals (Sweden)

    Dong Ki Park

    2013-01-01

    Full Text Available The anti-inflammatory activity of Antrodia camphorata (AC grown on germinated brown rice (CBR extract was evaluated in vitro and in vivo. CBR suppressed the release of nitric oxide (NO and prostaglandin (PG E2 from lipopolysaccharide-(LPS-stimulated RAW264.7 cells. CBR inhibited the level of inducible nitric oxide synthase (iNOS and cyclooxygenase-(COX-2 proteins, and it activated p38-MAPK, extracellular signal-related kinases (ERK, and NF-κB in LPS-stimulated RAW264.7 macrophages. LPS-induced tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 mRNA expression was reduced in CBR-treated RAW264.7 cells. In concert with in vitro data, CBR suppressed the levels of dextran-sulfate-sodium-(DSS-induced iNOS and COX-2 proteins in the colon tissue. CBR treatment inhibited activated p38-MAPK, ERK, and NF-κB proteins in the colon tissue of DSS-induced mice. TNF-α and IL-6 mRNA expression was reduced in DSS+CBR-treated mice. The disease activity index and histological scores were significantly lower in CBR-treated mice (500 mg/kg/day than in DSS-treated mice ( versus DSS. This is the first report of anti-inflammatory activity of CBR in DSS-induced acute colitis. These results suggest that CBR is a promising, potential agent for preventing acute colitis through the inhibition of NF-κB signaling and its upstream signaling molecules, including MAPKs.

  6. Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children.

    Science.gov (United States)

    Fitrolaki, Michaela-Diana; Dimitriou, Helen; Venihaki, Maria; Katrinaki, Marianna; Ilia, Stavroula; Briassoulis, George

    2016-08-01

    Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness.A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression.HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern.

  7. Effect of acute sleep deprivation and recovery on Insulin-like Growth Factor-I responses and inflammatory gene expression in healthy men.

    Science.gov (United States)

    Chennaoui, Mounir; Drogou, Catherine; Sauvet, Fabien; Gomez-Merino, Danielle; Scofield, Denis E; Nindl, Bradley C

    2014-01-01

    Acute sleep deprivation in humans has been found to increase inflammatory markers and signaling pathways in the periphery through a possible Toll-like receptor 4 (TLR-4). In addition, short duration sleep has been associated with low circulating total Insulin-like Growth Factor-I (IGF-I) concentrations. We aimed to determine whether a total sleep deprivation (TSD) protocol with recovery altered whole-blood gene expression of the proinflammatory cytokines TNF-α and IL-6, as well as TLR-4 expression, and to examine the relationship with circulating concentrations of the IGF-I system. Twelve healthy men participated in a five-day TSD (two control nights followed by one night of sleep deprivation and one night of recovery). Blood was sampled at 0800, before and after sleep deprivation (D2 and D4), and after recovery (D5). It is shown that 25 h of sleep deprivation (D4) induced significant increases in mRNA levels of TNF-α and its soluble receptor R1 (Precovery was sufficient to restore basal expression levels for TNF-α, sTNF-R1, TLR-4 and circulating IGF-I. Changes in TLR-4 mRNA levels during the protocol correlated positively with those of TNF-α and sTNF-R1 (r=0.393 and r=0.490 respectively), and negatively with circulating free IGF-I (r=-0.494). In conclusion, 25 h of sleep deprivation in healthy subjects is sufficient to induce transient and reversible genomic expression of the pro-inflammatory cytokine TNF-α and its R1 receptor, and its mediator TLR-4, with a possible link to IGF-I axis inhibition.

  8. Increased percentages of regulatory T cells are associated with inflammatory and neuroendocrine responses to acute psychological stress and poorer health status in older men and women.

    Science.gov (United States)

    Ronaldson, Amy; Gazali, Ahmad M; Zalli, Argita; Kaiser, Frank; Thompson, Stephen J; Henderson, Brian; Steptoe, Andrew; Carvalho, Livia

    2016-05-01

    The percentage of regulatory T cells (TRegs)-a subtype of T lymphocyte that suppresses the immune response-appears to be reduced in a number of stress-related diseases. The role of the TReg in stress-disease pathways has not yet been investigated. The aim of the study was to investigate the association between biological responsivity to acute psychosocial stress and the percentage of TRegs in healthy older adults. The secondary purpose was to measure the associations between TReg percentage and psychological and physical well-being in the participants. Salivary cortisol and plasma interleukin (IL)-6 samples were obtained from 121 healthy older men and women from the Whitehall II cohort following acute psychophysiological stress testing. Three years later at a follow-up visit, we measured TReg percentages and psychological and physical well-being were recorded using the Short Form 36 Health Survey and the Center for Epidemiologic Studies Depression Scale. Blunted cortisol responses (p = 0.004) and elevated IL-6 responses (p = 0.027) to acute psychophysiological stress were associated with greater TReg percentage independently of age, sex, BMI, smoking status, employment grade, time of testing, and baseline measures of cortisol and IL-6, respectively. Percentage of TRegs was associated cross-sectionally with lower physical (p = 0.043) and mental health status (p = 0.008), and higher levels of depressive symptoms (p = 0.002), independently of covariates. Increased levels of TRegs may act as a defence against increased inflammation and may be a pre-indication for chronically stressed individuals on the cusp of clinical illness.

  9. Anti-inflammatory and acute toxicity evaluation of aqueous infusion ...

    African Journals Online (AJOL)

    Background: Marrubium deserti de Noé, which is locally known as “Merriouet saharaui”, is widely used in Algeria as a traditional treatment of many ailments. In this study, the anti-inflammatory and acute toxicity of the aqueous infusion extract from aerial parts of Marrubium deserti were investigated. Meanwhile, acute oral ...

  10. Local up-regulation of interferon-γ (IFN-γ) following disc herniation is involved in the inflammatory response underlying acute lumbar radicular pain.

    Science.gov (United States)

    Moen, Gunn-Helen; Moen, Aurora; Schistad, Elina I; Gjerstad, Johannes

    2017-09-01

    Lumbar radicular pain after disc herniation may be associated with release of pro-inflammatory cytokines from nucleus pulposus (NP) tissue. In the present study we examined the role of interferon-γ (IFN-γ) and cluster of differentiation 68 (CD68) in the acute phase of this process. First, in an animal model mimicking the clinical situation after disc herniation, the role of IFN-γ close to the dorsal nerve roots was studied. Next, in patients with lumbar radicular pain due to disc herniation, we examined how two single nucleotide polymorphisms (SNPs; rs2069705 and rs2069718) are important for the IFN-γ expression influenced the pain behavior. The animal data demonstrated a significant increase in the nociceptive activity at the spinal level after local application of NP and IFN-γ onto the dorsal nerve roots. A positive correlation between IFN-γ and CD68 in the NP tissue was also demonstrated. In the patients, a significant increase in Oswestry Disability Index (ODI) score was observed in carriers of the IFN-γ SNPs; rs2069705 A and rs2069718 G alleles. The present data suggest that IFN-γ close to the dorsal nerve roots may contribute to the pathogenesis, the nociceptive activity and the pain behavior following lumbar disc herniation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. The Systemic Inflammatory Response Syndrome (SIRS)--number and type of positive criteria predict interventions and outcomes in acute surgical admissions.

    Science.gov (United States)

    Stephenson, James A; Gravante, Gianpiero; Butler, Nicholas A; Sorge, Roberto; Sayers, Rob D; Bown, Matt J

    2010-11-01

    Systemic inflammatory response syndrome (SIRS) is a syndrome that reflects the widespread activation of inflammatory pathways. The goal of this study was to find whether the presence or absence of SIRS on emergency surgical admissions is related to the subsequent clinical outcome in terms of in-hospital interventions, length of stay, and mortality. The presence of SIRS at admission, final diagnosis of the underlying disease, treatments, and clinical outcomes were prospectively recorded for 1 month. Comparisons of interventions and outcomes were performed between SIRS+ vs. SIRS- patients. In patients with SIRS, the contribution of each positive criterion was evaluated with regards to mortality. A total of 179 patients were recruited. The prevalence of SIRS at admission was 35.2%. SIRS+ patients required less diagnostic procedures compared with SIRS- (28.6% vs. 34.5%) but had more therapeutic interventions (39.7% vs. 16.4%), surgical interventions (33.3% vs. 3.4%), intensive treatments (11.1% vs. 0.9%; p SIRS+ patients with four positive criteria had more surgical interventions, intensive treatments, and fatal outcomes compared with the others. Of importance the most influent factor was the respiratory rate followed by the white cell count and the heart rate/temperature. Patients with SIRS at admission apparently receive more interventions, have longer length of stay, and increased mortality than those patients without SIRS. These findings require separate validation in a larger cohort study.

  12. Features of the response to inflammatory process in children with high and low intensity of free radical oxidations in lymphocytes during the acute period of the disease in various ethnic groups

    Directory of Open Access Journals (Sweden)

    V. V. Ivanova

    2012-01-01

    Full Text Available Acute phase response represents a constellation of local and systemic reactions of the organism to the tissue damage caused by various reasons – infection, trauma, inflammation, tumor growth. So-called proteins of acute phase have a special value among the factors causing some changes in the case of inflammation. In the article the features of acute phase response to the inflammation and regulating role of adaptation hormones in the case of acute respiratory infection complicated by pneumonia in children living in the conditions of Far North (Yakutia among the native population and the arrived one werer characterized. 112 children with acute respiratory infection accompanied by pneumonia and 42 practically healthy ones have been examined in the conditions of Far North. Both Russian and local population is forced to fight with pneumonia by the activation of free radical oxidation, i.e. usage of «respiratory explosion» reactions to get protected against inflammatory processes. The intensity difference in the biochemical response among the members of the two ethnic groups of patients is identified. Some considerable changes in С-reactive protein level, especially among Russians in the group with a high level of free radical oxidation (10 times above normal level are noted. Higher level of α-2-macroglobulin among children with a low level of free radical oxidation is also observed in the group of Russian children. The levels of transferrin and prealbumin are characterized by a valid increase only during the period of reconvalescence, after their synthesis activation by glucocorticoids the level of which is already increased during the acute period. The conducted research has confirmed valid shifts of adaptation hormone level, acute phase proteins and free radical oxidation processes in blood of children with cute respiratory infection accompanied by pneumonia in the conditions of Far North. More expressed

  13. Acute phase inflammatory markers in patients with non-steroidal anti-inflammatory drugs (NSAIDs)-induced acute urticaria/angioedema and after aspirin challenge.

    Science.gov (United States)

    Kasperska-Zając, A; Grzanka, A; Czecior, E; Misiolek, M; Rogala, B; Machura, E

    2013-08-01

    Active chronic urticaria, identified as a mast cell- and basophil-dependent inflammatory disorder of the skin is able to elicit acute phase response (APR). However, systemic inflammatory response in different types of urticaria is poorly characterized. To determine APR pattern in a clearly defined group of patients with acute urticaria and/or angioedema - induced by NSAIDs. Plasma IL-6 and serum C-reactive protein (CRP) concentrations were studied in 17 patients with NSAIDs-induced acute urticaria/angioedema (NSAIDsAU) and in 20 healthy controls. Eleven patients who used NSAIDs were presented at the emergency room with acute urticaria/angioedema while the remaining six manifested the symptoms during the aspirin challenge test. Patients were examined in a dynamic manner: during the acute phase, and next, after subsidence of the symptoms. CRP and IL-6 concentrations increased significantly in patients with NSAIDsAU as compared with their asymptomatic period and the healthy subjects. In addition, NSAIDsAU patients showed elevated concentration of the biomarkers following aspirin provocation with the baseline values recovered in the asymptomatic period. These results indicate that an acute systemic inflammatory response is activated in patients with NSAIDs-induced urticaria and/or angioedema. The study supports the evidence proving that up-regulation of CRP and IL-6 in urticaria/angioedema does not necessarily reflect any concomitant infection or other inflammatory processes, but may be due to the disease itself. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

  14. Acute Inflammatory Demyelinating Polyradiculo-neuropathy following Antirabies Vaccine

    Directory of Open Access Journals (Sweden)

    Bindu M

    2005-01-01

    Full Text Available Newer generation cell culture anti-rabies vaccines have become the preferred choice because of the paucity of the neurological complications. We report a case of acute inflammatory polyradiculo-neuropathy following the administration of purified chick embryo cell culture anti-rabies baccine for post exposure prophylaxis.

  15. inflammatory drugs fail to enhance healing of acute hamstring

    African Journals Online (AJOL)

    The effects of two non-steroidal anti-inflammatory drugs. (NSAIDs), meclofenamate and diclofenac, in combination with physiotherapy modalities on the rate of healing of acute hamstring muscle tears were studied in a double- blind, placebo-controlled trial. Forty-four of the 75 patients with this injury recruited were assessed ...

  16. Non-steroidal anti-inflammatory drugs for acute gout

    NARCIS (Netherlands)

    van Durme, Caroline M. P. G.; Wechalekar, Mihir D.; Buchbinder, Rachelle; Schlesinger, Naomi; van der Heijde, Désirée; Landewé, Robert B. M.

    2014-01-01

    Background Gout is an inflammatory arthritis that is characterised by the deposition of monosodium urate crystals in synovial fluid and other tissues. The natural history of articular gout is generally characterised by three periods: asymptomatic hyperuricaemia, episodes of acute gout and chronic

  17. Evaluation of acute toxicity and anti-inflammatory effects of ...

    African Journals Online (AJOL)

    It was further fractionated in sequence to n-hexane (BSH), chloroform (BSC) and methanol (BSM) soluble fractions. Acute toxicity was evaluated by oral administration of plant and hind paw induced-edema method in rats was used for the anti-inflammatory evaluation. Results: The BSE was found safe up to the dose level of ...

  18. Anti-inflammatory responses of resveratrol.

    Science.gov (United States)

    Das, Samarjit; Das, Dipak K

    2007-09-01

    Resveratrol (trans-3,4',5-trihydroxystilbene), a natural polyphenolic, non-flavonoid antioxidant, is a phytoalexin found in many plants including grapes, nuts and berries. Recent studies have documented that resveratrol has various health benefits, such as cardiovascular and cancer preventive properties. However, the experimental basis for such health benefit is not fully understood. One of the possible mechanisms for its protective activities is by down regulation of the inflammatory responses. That includes the inhibition of synthesis and release of pro-inflammatory mediators, modifications of eicosanoid synthesis, inhibition of some activated immune cells, or inhibiting the enzymes, such as cyclooxygenase-1 (COX-1) or cyclooxygenase-2 (COX-2), which are responsible for the synthesis of pro-inflammatory mediators through the inhibitory effect of resveratrol on transcription factors like nuclear factor kappaB (NFkappaB) or activator protein-1 (AP-1). Being a phenolic compound, resveratrol certainly possesses a low bioavailability and most importantly, a rapid clearance from the plasma. Recent growing interest in varying protective nature of resveratrol may clinically also hold a respectable position as a better alternative for anti-inflammatory drugs. The purpose of this review is to provide evidence that resveratrol exhibits potent anti-inflammatory activity and also to explain the underling mechanism for both resveratrol- induced cardioprotective and anti-inflammatory properties. While it is true that the cardioprotective properties of resveratrol are likely attributable, at least in part, to its anti-inflammatory properties, the mechanisms discussed address foremost mechanisms for the anti-inflammatory activity which, in turn, is responsible for cardioprotection.

  19. Systemic Inflammatory Response and Adhesion Molecules

    Directory of Open Access Journals (Sweden)

    L. V. Molchanova

    2005-01-01

    Full Text Available The lecture presents the materials of foreign studies on the mechanisms responsible for the formation of a systemic inflammatory response syndrome (SIRS. The hypotheses accounting for the occurrence of SIRS in emergencies are described. Adhesion molecules (AM and endothelial dysfunction are apparent to be involved in the inflammatory process, no matter what the causes of SIRS are. The current classification of AM and adhesion cascades with altered blood flow is presented. There are two lines in the studies of AM. One line is to measure the concentration of AM in the plasma of patients with emergencies of various etiology. The other is to study the impact of antiadhesion therapy on the alleviation of the severity of terminal state and its outcome. The studies provide evidence for that an adhesive process is a peculiar prelude to a systemic inflammatory response.

  20. Swine influenza H1N1 virus induces acute inflammatory immune responses in pig lungs: a potential animal model for human H1N1 influenza virus.

    Science.gov (United States)

    Khatri, Mahesh; Dwivedi, Varun; Krakowka, Steven; Manickam, Cordelia; Ali, Ahmed; Wang, Leyi; Qin, Zhuoming; Renukaradhya, Gourapura J; Lee, Chang-Won

    2010-11-01

    Pigs are capable of generating reassortant influenza viruses of pandemic potential, as both the avian and mammalian influenza viruses can infect pig epithelial cells in the respiratory tract. The source of the current influenza pandemic is H1N1 influenza A virus, possibly of swine origin. This study was conducted to understand better the pathogenesis of H1N1 influenza virus and associated host mucosal immune responses during acute infection in humans. Therefore, we chose a H1N1 swine influenza virus, Sw/OH/24366/07 (SwIV), which has a history of transmission to humans. Clinically, inoculated pigs had nasal discharge and fever and shed virus through nasal secretions. Like pandemic H1N1, SwIV also replicated extensively in both the upper and lower respiratory tracts, and lung lesions were typical of H1N1 infection. We detected innate, proinflammatory, Th1, Th2, and Th3 cytokines, as well as SwIV-specific IgA antibody in lungs of the virus-inoculated pigs. Production of IFN-γ by lymphocytes of the tracheobronchial lymph nodes was also detected. Higher frequencies of cytotoxic T lymphocytes, γδ T cells, dendritic cells, activated T cells, and CD4+ and CD8+ T cells were detected in SwIV-infected pig lungs. Concomitantly, higher frequencies of the immunosuppressive T regulatory cells were also detected in the virus-infected pig lungs. The findings of this study have relevance to pathogenesis of the pandemic H1N1 influenza virus in humans; thus, pigs may serve as a useful animal model to design and test effective mucosal vaccines and therapeutics against influenza virus.

  1. [Effect of Acupuncture on Inflammatory Cytokines in Patients with Acute Pelvic Inflammatory Disease].

    Science.gov (United States)

    Wu, Dan; Guo, Li-Yan; Lu, Pei-Si

    2018-01-25

    To observe the effect of acupuncture on inflammatory indices and symptoms in patients with acute pelvic inflammatory disease, and investigate its mechanism. Seventy-nine patients with acute pelvic inflammatory disease were randomly assigned to a control group ( n =37) given conventional treatment and an observation group ( n =42) given conventional treatment and acupuncture therapy. In the observation group, acupionts of Zhongji(CV 3), Guanyuan(CV 4), Zigong(EX-CA 1), Zusanli(ST 36), Sanyinjiao(SP 6), etc. were selected. Each group received treatment once daily, for a total of 7 days. Tumor necrosis factor (TNF)-α, interleukin (IL)-10 and C-reactive protein (CRP) in the serum, white blood cell (WBC) and neutrophil counts, size of pelvic mass and depth of pelvic effusion, and clinical symptoms were assayed pretreatment and on days 3 and 7. WBC and neutrophils were significantly decreased after treatment in both groups ( P pelvic mass and depth of effusion were less in both groups ( P inflammatory markers in patients with acute pelvic inflammatory disease, and improve clinical symptoms.

  2. Effect of Probiotic Administration on Acute Inflammatory Pain

    Directory of Open Access Journals (Sweden)

    Shadnoush

    2016-11-01

    Full Text Available Background Acute inflammatory pain causes by direct stimulation of nociceptors and release of inflammatory mediators and cytokines. Probiotics are capable to modulate the immune system, down regulate the inflammatory mediators, and increase regulatory and anti-inflammatory cytokines. Objectives The aim of this study was to examine the effect of oral administration of probiotics on behavioral, cellular and molecular aspects of acute inflammatory pain in male rats. Methods Adult male Wistar rats (200 - 220 g were selected and randomly divided into 7 experimental groups (CFA, CFA control, CFA + vehicle (distilled water, CFA + 3 doses of probiotics, CFA + indomethacin and each group was divided into 3 subgroups based on different time points (days 0, 3, and 7 (n = 6 rats, each group. Complete Freund’s adjuvant (CFA-induced arthritis (AA was caused by a single subcutaneous injection of CFA into the rats’ left hind paw on day 0. Different doses of probiotics (1/250, 1/500 and 1/1000 (109 CFU/g was administered daily (gavage after the CFA injection. Blood samples were taken from the vessel retro-orbital corners of rat’s eyes. After behavioral and inflammatory tests, the lumbar segments of rat’s spinal cord (L1 - L5 were removed. Hyperalgesia, edema, serum TNF-α and IL-1β levels and NF-κB expression were assessed on days 0, 3, and 7 of the study. Results The results of this study showed the role of effective dose of probiotics (1/500 in reducing edema (P = 0.0009, hyperalgesia (P = 0.0002, serum levels of TNF-α (P = 0.0004 and IL-1β (P = 0.0004 and NF-κB expression (P = 0.0007 during the acute phase of inflammatory pain caused by CFA. Conclusions It seems that an effective dose of probiotics due to its direct effects on inhibition of intracellular signaling pathways and pro-inflammatory cytokines can alleviate inflammatory symptoms and pain in the acute phase.

  3. Colchicine Acutely Suppresses Local Cardiac Production of Inflammatory Cytokines in Patients With an Acute Coronary Syndrome

    Science.gov (United States)

    Martínez, Gonzalo J; Robertson, Stacy; Barraclough, Jennifer; Xia, Qiong; Mallat, Ziad; Bursill, Christina; Celermajer, David S; Patel, Sanjay

    2015-01-01

    Background Interleukin (IL)-1β, IL-18, and downstream IL-6 are key inflammatory cytokines in the pathogenesis of coronary artery disease. Colchicine is believed to block the NLRP3 inflammasome, a cytosolic complex responsible for the production of IL-1β and IL-18. In vivo effects of colchicine on cardiac cytokine release have not been previously studied. This study aimed to (1) assess the local cardiac production of inflammatory cytokines in patients with acute coronary syndromes (ACS), stable coronary artery disease and in controls; and (2) determine whether acute administration of colchicine inhibits their production. Methods and Results Forty ACS patients, 33 with stable coronary artery disease, and 10 controls, were included. ACS and stable coronary artery disease patients were randomized to oral colchicine treatment (1 mg followed by 0.5 mg 1 hour later) or no colchicine, 6 to 24 hours prior to cardiac catheterization. Blood samples from the coronary sinus, aortic root (arterial), and lower right atrium (venous) were collected and tested for IL-1β, IL-18, and IL-6 using ELISA. In ACS patients, coronary sinus levels of IL-1β, IL-18, and IL-6 were significantly higher than arterial and venous levels (P=0.017, Colchicine administration significantly reduced transcoronary gradients of all 3 cytokines in ACS patients by 40% to 88% (P=0.028, 0.032, and 0.032, for IL-1β, IL-18, and IL-6, respectively). Conclusions ACS patients exhibit increased local cardiac production of inflammatory cytokines. Short-term colchicine administration rapidly and significantly reduces levels of these cytokines. PMID:26304941

  4. The role of whole blood impedance aggregometry and its utilisation in the diagnosis and prognosis of patients with systemic inflammatory response syndrome and sepsis in acute critical illness.

    Directory of Open Access Journals (Sweden)

    Gareth R Davies

    Full Text Available OBJECTIVE: To assess the prognostic and diagnostic value of whole blood impedance aggregometry in patients with sepsis and SIRS and to compare with whole blood parameters (platelet count, haemoglobin, haematocrit and white cell count. METHODS: We performed an observational, prospective study in the acute setting. Platelet function was determined using whole blood impedance aggregometry (multiplate on admission to the Emergency Department or Intensive Care Unit and at 6 and 24 hours post admission. Platelet count, haemoglobin, haematocrit and white cell count were also determined. RESULTS: 106 adult patients that met SIRS and sepsis criteria were included. Platelet aggregation was significantly reduced in patients with severe sepsis/septic shock when compared to SIRS/uncomplicated sepsis (ADP: 90.7±37.6 vs 61.4±40.6; p<0.001, Arachadonic Acid 99.9±48.3 vs 66.3±50.2; p = 0.001, Collagen 102.6±33.0 vs 79.1±38.8; p = 0.001; SD ± mean. Furthermore platelet aggregation was significantly reduced in the 28 day mortality group when compared with the survival group (Arachadonic Acid 58.8±47.7 vs 91.1±50.9; p<0.05, Collagen 36.6±36.6 vs 98.0±35.1; p = 0.001; SD ± mean. However haemoglobin, haematocrit and platelet count were more effective at distinguishing between subgroups and were equally effective indicators of prognosis. Significant positive correlations were observed between whole blood impedance aggregometry and platelet count (ADP 0.588 p<0.0001, Arachadonic Acid 0.611 p<0.0001, Collagen 0.599 p<0.0001 (Pearson correlation. CONCLUSIONS: Reduced platelet aggregometry responses were not only significantly associated with morbidity and mortality in sepsis and SIRS patients, but also correlated with the different pathological groups. Whole blood aggregometry significantly correlated with platelet count, however, when we adjust for the different groups we investigated, the effect of platelet count appears to be non-significant.

  5. Plasma inflammatory biomarkers response to aerobic versus ...

    African Journals Online (AJOL)

    Plasma inflammatory biomarkers response to aerobic versus resisted exercise training for chronic obstructive pulmonary disease patients. ... Recent studies proved that morbidity and mortality of COPD is related to systemic inflammation as it contributes to the pathogenesis of atherosclerosis and cardiovascular disease.

  6. Plasma inflammatory biomarkers response to aerobic versus ...

    African Journals Online (AJOL)

    Plasma inflammatory biomarkers response to aerobic versus resisted exercise training for chronic obstructive pulmonary ... Department of Physical Therapy, Faculty of Applied Medical Sciences, King Abdulaziz University. 2. Department of Medical ... exercises were proved to improve immune system re- sponse17. Even low ...

  7. Acute inflammatory response to a foreign body in Calomys callosus Perfil de migração celular agudo induzido pela presença de corpo estranho em Calomys callosus

    Directory of Open Access Journals (Sweden)

    André Kipnis

    2008-07-01

    Full Text Available

    Calomys callosus are wild rodents present in the Brazilian savannas that were adapted to the laboratorial conditions. These animals are resistant to infections that induce chronic inflammatory responses (Trypanosoma cruzi and Paracoccidioides brasiliensis. The objective of this work was to characterize the acute inflammatory reaction, prompted by the subcutaneous implementation of a foreign body. Twenty seven C. callosus and thirty B10A mice received implant and were comparatively analyzed during 144 hours. Circular cover slides implanted in C. callosus showed predominance of macrophages and eosinophils whereas in the mice, the neutrophils followed by the macrophages were the migratory dominant cells (p <0.05. It was concluded that C. callosus present inflammatory mechanisms for the removal of foreign body different from the ones found in the other rodents as well as in the human beings.

     

    KEY WORDS: Acute inflammation, cover slip, granuloma, histology, wild rodents.

    Calomys callosus são roedores silvestres presentes no cerrado brasileiro, que foram adaptados às condições laboratoriais. Trata-se de animais que apresentam resistência às infecções que induzem respostas inflamatórias crônicas (Trypanosoma cruzi e Paracoccidioides brasiliensis. O objetivo deste trabalho foi caracterizar a reação inflamatória, na fase aguda, induzida pela implantação subcutânea de um corpo estranho. Vinte e sete C. callosus e trinta camundongos (B10A foram implantados e analisados comparativamente durante 144 horas. Lamínulas implantadas em C. callosus mostraram predomínio de macrófagos e eosinófilos, enquanto que, nos camundongos, os neutrófilos seguidos pelos macrófagos foram as células migratórias dominantes (p< 0,05. Conclui-se que os C. callosus

  8. Effects of Prolastin C (Plasma-Derived Alpha-1 Antitrypsin) on the acute inflammatory response in patients with ST-segment elevation myocardial infarction (from the VCU-alpha 1-RT pilot study)

    NARCIS (Netherlands)

    Abbate, A.; Tassell, B.W. Van; Christopher, S.; Abouzaki, N.A.; Sonnino, C.; Oddi, C.; Carbone, S.; Melchior, R.D.; Gambill, M.L.; Roberts, C.S.; Kontos, M.C.; Peberdy, M.A.; Toldo, S.; Vetrovec, G.W.; Biondi-Zoccai, G.; Dinarello, C.A.

    2015-01-01

    Alpha-1 antitrypsin (AAT) has broad anti-inflammatory and immunomodulating properties in addition to inhibiting serine proteases. Administration of human plasma-derived AAT is protective in models of acute myocardial infarction in mice. The objective of this study was to determine the safety and

  9. Acute pelvic inflammatory disease as a rare cause of acute small bowel obstruction.

    Science.gov (United States)

    Haumann, Alexandre; Ongaro, Sarah; Detry, Olivier; Meunier, Paul; Meurisse, Michel

    2018-03-21

    Small bowel obstruction (SBO) is a common presentation to emergency abdominal surgery. The most frequent causes of SBO are congenital, postoperative adhesions, abdominal wall hernia, internal hernia and malignancy. A 27-year-old woman was hospitalized because of acute abdominal pain, blockage of gases and stools associated with vomiting. Abdominal computed tomography showed an acute small bowel obstruction without any obvious etiology. In view of important abdominal pain and the lack of clear diagnosis, an explorative laparoscopy was performed. Diagnostic of pelvic inflammatory disease was established and was comforted by positive PCR for Chlamydia Trachomatis. Acute small bowel obstruction resulting from acute pelvic inflammatory disease, emerging early after infection, without any clinical or X-ray obvious signs was not described in the literature yet. This infrequent acute SBO etiology but must be searched especially when there is no other evident cause of obstruction in female patients. Early laparoscopy is mostly advised when there are some worrying clinical or CT scan signs.

  10. Chagas disease: modulation of the inflammatory response by acetylcholinesterase in hematological cells and brain tissue.

    Science.gov (United States)

    Silva, Aniélen D; Bottari, Nathieli B; do Carmo, Guilherme M; Baldissera, Matheus D; Souza, Carine F; Machado, Vanessa S; Morsch, Vera M; Schetinger, Maria Rosa C; Mendes, Ricardo E; Monteiro, Silvia G; Da Silva, Aleksandro S

    2018-01-01

    Chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. This enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. Thus, the aim of this study was to investigate whether Trypanosoma cruzi infection can alter the activity of acetylcholinesterase and acetylcholine levels in mice, and whether these alterations are linked to the inflammatory cholinergic signaling pathway. Twenty-four mice were divided into two groups: uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12). The animals developed acute disease with a peak of parasitemia on day 7 post-infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post-infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase activity, and histopathology were analyzed. In total blood and brain, acetylcholinesterase activity decreased at both times. On the other hand, acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with the control group. Infection by T. cruzi increased acetylcholine and nitric oxide levels and histopathological damage in the brain of mice associated to increased myeloperoxidase activity. Therefore, an intense inflammatory response in mice with acute Chagas disease in the central nervous system caused an anti-inflammatory response by the activation of the cholinergic inflammatory pathway.

  11. Wild skylarks seasonally modulate energy budgets but maintain energetically costly inflammatory immune responses throughout the annual cycle

    NARCIS (Netherlands)

    Hegemann, A.; Matson, K.D.; Versteegh, M.A.; Tieleman, B.I.

    2012-01-01

    A central hypothesis of ecological immunology is that immune defences are traded off against competing physiological and behavioural processes. During energetically demanding periods, birds are predicted to switch from expensive inflammatory responses to less costly immune responses. Acute phase

  12. Age differences in inflammatory and hypermetabolic postburn responses.

    Science.gov (United States)

    Jeschke, Marc G; Norbury, William B; Finnerty, Celeste C; Mlcak, Ronald P; Kulp, Gabriela A; Branski, Ludwik K; Gauglitz, Gerd G; Herndon, Blair; Swick, Aron; Herndon, David N

    2008-03-01

    The aim of this study was to identify contributors to morbidity and death in severely burned patients 4 years of age lost body weight and lean body mass. The inflammatory cytokine profile showed no differences between the 3 age groups, whereas liver size increased significantly in the 10- to 18-year-old group and was lowest in the 0- to 3.9-year-old group. Acute-phase protein and cortisol levels were significantly decreased in the toddler group, compared with the older children. Cardiac data indicated increased cardiac work and impaired function in the toddler group, compared with the other 2 age groups. Increased mortality rates for young children are associated with increased cardiac work and impaired cardiac function but not with the inflammatory and hypermetabolic responses.

  13. Can New Inflammatory Markers Improve the Diagnosis of Acute Appendicitis?

    DEFF Research Database (Denmark)

    Andersson, Manne; Rubér, Marie; Ekerfelt, Christina

    2014-01-01

    BACKGROUND: The diagnosis of appendicitis is difficult and resource consuming. New inflammatory markers have been proposed for the diagnosis of appendicitis, but their utility in combination with traditional diagnostic variables has not been tested. Our objective is to explore the potential of new...... inflammatory markers for improving the diagnosis of appendicitis.METHODS: The diagnostic properties of the six most promising out of 21 new inflammatory markers (interleukin [IL]-6, chemokine ligand [CXCL]-8, chemokine C-C motif ligand [CCL]-2, serum amyloid A [SAA], matrix metalloproteinase [MMP]-9......, and myeloperoxidase [MPO]) were compared with traditional diagnostic variables included in the Appendicitis Inflammatory Response (AIR) score (right iliac fossa pain, vomiting, rebound tenderness, guarding, white blood cell [WBC] count, proportion neutrophils, C-reactive protein and body temperature) in 432 patients...

  14. Neuroimmune regulation of inflammatory responses in inflammatory bowel disease

    NARCIS (Netherlands)

    Rijnierse, Anneke

    2006-01-01

    The term inflammatory bowel disease (IBD) is used to describe chronic inflammatory conditions of the gastro-intestinal tract. Patients suffer from abdominal pain, diarrhea, rectal bleeding and a substantial personal burden. The etiology of IBD is gradually being unraveled but remains a complex

  15. The systemic pro-inflammatory response in sepsis.

    Science.gov (United States)

    de Jong, Hanna Katrien; van der Poll, Tom; Wiersinga, Willem Joost

    2010-01-01

    The systemic inflammatory response syndrome (SIRS) is the predominantly cytokine-mediated, pro-inflammatory response of the host to invading pathogens and is considered the hallmark sign of sepsis. Molecular components of this response can be divided into cytokines, plasma cascades and acute phase proteins while the predominant cellular components are leukocytes and the endothelium. High-throughput genetic profiling studies have led to increased insights into leukocyte regulation during sepsis. New players in the pro-inflammatory cytokine network include interleukin-17, high-mobility group box-1 protein, macrophage migration inhibitory factor, the myeloid-related proteins Mrp8 and Mrp14, and soluble triggering receptor expressed on myeloid cells-1. Activation of coagulation with concurrent downregulation of anticoagulant systems and fibrinolysis are almost universally present in septic patients with SIRS. Increasing evidence points to an extensive cross-talk between inflammation and coagulation, in which the protease-activated cell receptors play an important role. Sepsis causes excessive activation of the complement system in which C5a plays a key part. Further dissection of the role of host-pathogen interactions, the cytokine network, the coagulation cascade, the complement system and their multidirectional interactions in sepsis will pave the way for new treatment targets that can modify the excessive and collective activation of all these systems. 2010 S. Karger AG, Basel.

  16. Role of Apoptosis in Amplifying Inflammatory Responses in Lung Diseases

    Directory of Open Access Journals (Sweden)

    E.P. Schmidt

    2010-01-01

    Full Text Available Apoptosis is an important contributor to the pathophysiology of lung diseases such as acute lung injury (ALI and chronic obstructive pulmonary disease (COPD. Furthermore, the cellular environment of these acute and chronic lung diseases favors the delayed clearance of apoptotic cells. This dysfunctional efferocytosis predisposes to the release of endogenous ligands from dying cells. These so-called damage-associated molecular patterns (DAMPs play an important role in the stimulation of innate immunity as well as in the induction of adaptive immunity, potentially against autoantigens. In this review, we explore the role of apoptosis in ALI and COPD, with particular attention to the contribution of DAMP release in augmenting the inflammatory response in these disease states.

  17. Anti-Inflammatory Properties of NAP in Acute Toxoplasma Gondii-Induced Ileitis in Mice.

    Science.gov (United States)

    Heimesaat, Markus M; Fischer, André; Kühl, Anja A; Göbel, Ulf B; Gozes, Illana; Bereswill, Stefan

    2015-09-01

    The octapeptide NAP has been shown to exert neuroprotective properties. Here, we investigated potential anti-inflammatory effects of NAP in an acute ileitis model. To address this, C57BL/6j mice were perorally infected with Toxoplasma gondii (day 0). Within 1 week postinfection (p.i.), placebo (PLC)-treated mice developed acute ileitis due to Th1-type immune responses. Mice that were subjected to intraperitoneal NAP treatment from day 1 until day 6 p.i., however, developed less distinct macroscopic and microscopic disease as indicated by less body weight loss, less distinct histopathological ileal changes, and lower ileal apoptotic, but higher proliferating cell numbers, less abundance of neutrophils, macrophages, monocytes, and T lymphocytes, but higher numbers of regulatory T cells in the ileal mucosa and lamina propria, and lower concentrations of pro-inflammatory mediators in the ilea as compared to PLC controls at day 7 p.i. Remarkably, NAP-mediated anti-inflammatory effects could also be observed in extra-intestinal compartments including liver and spleen. Strikingly, lower MCP-1, TNF, and IL-12p70 serum concentrations in NAP as compared to PLC-treated mice at day 7 p.i. indicate a pronounced systemic anti-inflammatory effect of NAP in acute ileitis. These findings provide first evidence for NAP as a potential novel treatment option in intestinal inflammation.

  18. [Effect of compound danshen dripping pill combined with intravenous transplantation of human umbilical cord blood mononuclear cells on local inflammatory response in the myocardium of rabbits with acute myocardial infarction].

    Science.gov (United States)

    Deng, Liu-xia; Yu, Guo-long; Al, Qi; Yuan, Chun-ju

    2013-11-01

    To investigate effect of Compound Danshen Dripping Pill (CDDP) on the inflammatory response of the myocardium of acute myocardial infarction (AMI) rabbits, to observe the therapeutic effect of CDDP combined intravenous transplantation of human umbilical cord blood mononuclear cells (HUCBMCs) on inflammatory response, pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) , and heart function in the myocardium of AMI rabbits, and to explore the possible protective mechanisms of the combined therapy. The AMI model was successfully established by ligation of the left anterior coronary artery (LAD) in 40 healthy rabbits.Then they were randomly divided into four groups, i.e., the control group, the CDDP group, the transplantation group, and the combined group, 10 in each group. Rabbits in the control group received intravenous injection of 0.5 mL normal saline via ear vein within 24 h after AMI and then intragastric infusion of normal saline at 5 mL per day. Rabbits in the CDDP group received intravenous injection of 0.5 mL normal saline via ear vein within 24 h after AMI and then intragastric infusion of solution obtained by solving 270 mg CDDP in 5 mL normal saline per day. Rabbits in the transplantation group received intravenous injection of 0.5 mL normal saline labeled with green fluorescent protein (GFP) containing 3 x 10(7) of HUCBMCs via ear vein within 24 h after AMI and then intragastric infusion of normal saline at 5 mL per day. Rabbits in the combined group received intravenous injection of 0.5 mL normal saline labeled with GFP containing 3 x 10(7) of HUCBMCs via ear vein within 24 h after AMI and then intragastric infusion of solution obtained by solving 270 mg CDDP in 5 mL normal saline per day. At week 1 and 4 after treatment, cardiac function indices such as left ventricular fractional shorting (LVFS) and left ventricular ejection fraction (LVEF) were performed by echocardiography; the number of transplanted cells in the myocardium was found

  19. Effect of ghrelin on inflammatory response in lung contusion

    Directory of Open Access Journals (Sweden)

    Berrak Guven

    2013-02-01

    Full Text Available The purpose of this study was to investigate the effects of ghrelin on inflammatory response and tissue damage following trauma-induced acute lung injury. Thirty male wistar albino rats (300–400 g were randomly assigned into three groups: control group (n = 6, lung contusion plus saline (saline-treated, n = 12, and lung contusion plus ghrelin (ghrelin-treated, n = 12. Saline- or ghrelin-treated traumatic rats were sacrificed at two time points (24 and 72 hours after lung contusion. Blood was collected for the analysis of serum adenosine deaminase (ADA. Tissue transforming growth factor-beta 1 (TGF-β1 and matrix metalloproteinase-2 (MMP-2 levels were measured by enzyme-linked immunosorbent assay and histopathological examination was performed on the lung tissue samples. Our results indicated that ghrelin significantly reduced morphologic damages. Serum ADA activities were significantly decreased after lung contusion and this decline started early with ghrelin treatment. TGF-β1 and MMP-2 levels in lung tissue were elevated at 72 hours after lung contusion and treatment with ghrelin significantly increased TGF-β1 level and reduced MMP-2 level. In conclusion, our study demonstrates that acute lung injury initiated proinflammatory responses and ghrelin administration showed an anti-inflammatory effect in lung contusion.

  20. Effects of gabapentin in acute inflammatory pain in humans

    DEFF Research Database (Denmark)

    Werner, M U; Perkins, F M; Holte, Kathrine

    2001-01-01

    BACKGROUND AND OBJECTIVES: The aim of the study was to examine the analgesic effects of the anticonvulsant, gabapentin, in a validated model of acute inflammatory pain. METHODS: Twenty-two volunteers were investigated in a double-blind, randomized, placebo-controlled cross-over study. Gabapentin 1...... stimuli (visual analog scale [VAS]), assessments of thermal and mechanical detection thresholds, and areas of secondary hyperalgesia. Side effects drowsiness and postural instability were assessed by subjective ratings (VAS). RESULTS: The burn injury induced significant primary and secondary hyperalgesia...

  1. Acute Inflammatory Demyelinating Neuropathy : Immunoglobulin And Immune Complex Profile

    Directory of Open Access Journals (Sweden)

    Shripad A

    2003-01-01

    Full Text Available Serum immunoglobulins (IgG, IgA and IgM and immune complexes IgG (IcG were measured in 58 cases of acute inflammatory demyelinating neuropathy, popularly known as Guillian Barre′ syndrome, and in 30 healthy controls using single radial immunodiffusion assay. Immunoglobulin and immune complex levels were significantly elevated in patients as compared to controls. The increased levels of immunoglobulins and immune complexes may contribute to the pathogenesis of the disease and provide rationale for therapeutic plasmapheresis.

  2. Inflammatory response to strenuous muscular exercise in man

    Directory of Open Access Journals (Sweden)

    G. Camus

    1993-01-01

    Full Text Available Based on the humoral and cellular changes occurring during strenuous muscular work in humans, the concept of inflammatory response to exercise (IRE is developed. The main indices of IRE consist of signs of an acute phase response, leucocytosis and leucocyte activation, release of inflammatory mediators, tissue damage and cellular infiltrates, production of free radicals, activation of complement, and coagulation and fibrinolytic pathways. Depending on exercise intensity and duration, it seems likely that muscle and/or associated connective tissue damage, contact system activation due to shear stress on endothelium and endotoxaemia could be the triggering mechanisms of IRE. Although this phenomenon can be considered in most cases as a physiological process associated with tissue repair, exaggerated IRE could have physiopathological consequences. On the other hand, the influence of several factors such as age, sex, training, hormonal status, nutrition, anti-inflammatory drugs, and the extent to which IRE could be a potential risk for subjects undergoing intense physical training require further study.

  3. Peripheral analgesic effects of ketamine in acute inflammatory pain

    DEFF Research Database (Denmark)

    Pedersen, J L; Galle, T S; Kehlet, H

    1998-01-01

    BACKGROUND. This study examined the analgesic effect of local ketamine infiltration, compared with placebo and systemic ketamine, in a human model of inflammatory pain. METHODS: Inflammatory pain was induced by a burn (at 47 degrees C for 7 min; wound size, 2.5 x 5 cm) on the calf in 15 volunteers.......02). Secondary hyperalgesia and suprathreshold pain responses to heat and mechanical stimuli were not significantly affected by local ketamine. No difference between local ketamine and placebo could be detected 1 h and 2 h after the burn. CONCLUSIONS: Ketamine infiltration had brief local analgesic effects...

  4. Comparison of host inflammatory responses between calcium-silicate base material and IRM

    Directory of Open Access Journals (Sweden)

    Chi-Jr Hung

    2014-06-01

    Conclusion: These three cements could be considered to be biocompatible even though they induced different inflammatory responses and tissue changes during implantation tests in rats. CS cement did not induce acute inflammation and tissue responses similar to those reported for MTA.

  5. Scorpion Venom and the Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Vera L. Petricevich

    2010-01-01

    Full Text Available Scorpion venoms consist of a complex of several toxins that exhibit a wide range of biological properties and actions, as well as chemical compositions, toxicity, and pharmacokinetic and pharmacodynamic characteristics. These venoms are associated with high morbility and mortality, especially among children. Victims of envenoming by a scorpion suffer a variety of pathologies, involving mainly both sympathetic and parasympathetic stimulation as well as central manifestations such as irritability, hyperthermia, vomiting, profuse salivation, tremor, and convulsion. The clinical signs and symptoms observed in humans and experimental animals are related with an excessive systemic host inflammatory response to stings and stings, respectively. Although the pathophysiology of envenomation is complex and not yet fully understood, venom and immune responses are known to trigger the release of inflammatory mediators that are largely mediated by cytokines. In models of severe systemic inflammation produced by injection of high doses of venom or venoms products, the increase in production of proinflammatory cytokines significantly contributes to immunological imbalance, multiple organ dysfunction and death. The cytokines initiate a cascade of events that lead to illness behaviors such as fever, anorexia, and also physiological events in the host such as activation of vasodilatation, hypotension, and increased of vessel permeability.

  6. Age-associated alterations in the time-dependent profile of pro- and anti-inflammatory proteins within the hippocampus in response to acute exposure to interleukin-1β.

    Science.gov (United States)

    Hopp, Sarah C; Royer, Sarah; Brothers, Holly M; Kaercher, Roxanne M; D'Angelo, Heather; Bardou, Isabelle; Wenk, Gary L

    2014-02-15

    The pro-inflammatory cytokine IL-1β is known to play a role in several models of aging, neuroinflammation, and neurodegenerative diseases. Here, we document a detailed time- and age-dependent pattern of pro- and anti-inflammatory biomarkers following bilateral intrahippocampal injection of interleukin-1β. During the first 12h several pro- and anti-inflammatory cytokines increased in the aged (24 mo old) rats, some of which returned to baseline levels by 24h post-injection while others remained elevated for 72 h post-injection. In contrast, no such increases were observed in the young (3 mo old) rats. Interestingly, young rats up-regulated mRNA of two pro-inflammatory cytokines, interleukin-1β and tumor necrosis factor-α, but did not translate these transcripts into functional proteins, which may be related to expression of suppressor of cytokine signaling type-2. These results contribute to our understanding of how neuroinflammation may contribute to the pathogenesis of age-related neurodegenerative disorders due to an age-related bias towards a hyper-reactive immune response that is not selective for a pro- or anti-inflammatory phenotype following an inflammatory stimulus. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Papanicolaou smears and cervical inflammatory cytokine responses

    Directory of Open Access Journals (Sweden)

    Shapiro Samual

    2007-04-01

    Full Text Available Abstract In a case-control study among 2064 South African women to investigate the risk of clinically invasive cancer of the cervix, we found a marked reduction in the risk of cervical cancer among women who gave a history of ever having undergone even a single Pap smear, and a statistically significant decline in the HPV positivity rate correlated with the lifetime number of Pap smears received. HPV infections and their associated low-grade lesions commonly regress, indicating that most often there is an effective host immune response against HPV infection. We hypothesized that act of performing a Pap smear is associated with inflammatory responses at the site of trauma, the cervix, and that this inflammatory signalling may be an immunological factor initiating these productive anti-HPV responses. In the present study, a randomized controlled trial, we enrolled 80 healthy young women to investigate the impact of performing a Pap smear on cervical inflammation. Forty one women, in the intervention group, received a Pap smear at enrollment and cervicovaginal lavages (CVLs were collected at baseline and 2 weeks later. Thirty nine women received no intervention at enrollment (control group but CVLs were collected at enrolment and 2 weeks later. We assessed various markers of inflammation including IL-12 p70, TNF-α, IL-8, IL-6, IL-10, and IL-1β in CVL specimens. While CVL levels of IL-8, IL-1β and IL-6 remained unchanged following a Pap smear, markers of cell mediated immunity (IL-12 p70 and TNF-α and T cell regulation (IL-10 were significantly elevated.

  8. Inflammatory response in transapical transaortic valve replacement.

    Science.gov (United States)

    Goetzenich, A; Roehl, A; Spillner, J; Haushofer, M; Dohmen, G; Tewarie, L; Moza, A

    2011-12-01

    Transapical aortic valve implantation (TA-AVI) has become a fast growing alternative to conventional aortic valve replacement (cAVR) particularly for patients burdened with serious comorbidities. We investigated whether the inflammatory response triggered by TA-AVI reflects the less invasive nature of this procedure. In this prospective observational study 25 patients undergoing aortic valve replacement (AVR; 15 cAVR and 10 TA-AVI) were included. Serial plasma cytokine concentrations (IL-6, IL-8, and IL-10) were measured by commercially available enzyme-linked immunosorbent assay kits at six different time points before, during, and after surgery. Plasma levels of all three cytokines increased during and after both procedures and returned to baseline before the patient's discharge. Peak values of IL-6 were 258 ± 113 pg/mL in AVR patients versus 111 ± 101 pg/mL in TA-AVI patients and were reached 12 hours after surgery. For IL-8, peak values were 51 ± 29 pg/mL 1 hour after surgery in AVR patients versus 15 ± 20 pg/mL on wound closure in TA-AVI patients. Plasma levels of IL-6 and IL-8 were significantly reduced in the TA-AVI group as compared with cAVR. IL-10 is markedly activated in both groups yet its induction is more prominent in AVR patients with peak values of 51 ± 28 pg/mL for AVR versus 24 ± 18 pg/mL for TA-AVI on wound closure. TA-AVI compared with cAVR results in a significant reduction but not elimination of a systemic inflammatory response, which is attributable to cardiopulmonary bypass-dependent and bypass-independent factors. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Anti-inflammatory treatment for carditis in acute rheumatic fever.

    Science.gov (United States)

    Cilliers, Antoinette; Adler, Alma J; Saloojee, Haroon

    2015-05-28

    Rheumatic heart disease remains an important cause of acquired heart disease in developing countries. Although prevention of rheumatic fever and management of recurrences have been well established, optimal management of active rheumatic carditis remains unclear. This is an update of a review published in 2003, and previously updated in 2009 and 2012. To assess the effects, both harmful and beneficial, of anti-inflammatory agents such as aspirin, corticosteroids and other drugs in preventing or reducing further valvular damage in patients with acute rheumatic fever. We searched the Cochrane Central Register of Controlled Trials (2013, Issue 9 of 12), MEDLINE (Ovid, 1948 to 2013 October Week 1), EMBASE (Ovid, 1980 to 2013 Week 41) and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to 17 October 2013). We last searched Index Medicus (1950 to April 2001) in 2001. We checked reference lists of identified studies and applied no language restrictions. Randomised controlled trials comparing anti-inflammatory agents (e.g. aspirin, steroids, immunoglobulins, pentoxifylline) versus placebo or controls, or comparing any of the anti-inflammatory agents versus one another, in adults and children with acute rheumatic fever diagnosed according to Jones, or modified Jones, criteria. The presence of cardiac disease one year after treatment was the major outcome criterion selected. Two review authors extracted data and assessed risk of bias using the methodology outlined in the Cochrane Handbook of Systematic Reviews of Interventions. Standard methodological procedures as expected by The Cochrane Collaboration were used. No new studies were included in this update. Eight randomised controlled trials involving 996 people were selected for inclusion in the review. Researchers compared several steroidal agents such as corticotrophin, cortisone, hydrocortisone, dexamethasone, prednisone and intravenous immunoglobulin versus aspirin, placebo or no treatment. Six

  10. The systemic inflammatory response syndrome predicts short-term outcome after transapical transcatheter aortic valve implantation

    NARCIS (Netherlands)

    Rettig, Thijs C D; Rigter, Sander; Nijenhuis, Vincent J.; Van Kuijk, Jan Peter; Ten Berg, Jurriën M.; Heijmen, Robin H.; Van De Garde, Ewoudt M W; Noordzij, Peter G.

    2015-01-01

    Objective Despite the minimally invasive nature of transcatheter aortic valve implantation (TAVI), the incidence of acute kidney injury (AKI) and mortality is of major concern. Several studies showed that outcome was influenced by the systemic inflammatory response syndrome (SIRS) in patients

  11. High-intensity interval training induces a modest systemic inflammatory response in active, young men

    Science.gov (United States)

    Zwetsloot, Kevin A; John, Casey S; Lawrence, Marcus M; Battista, Rebecca A; Shanely, R Andrew

    2014-01-01

    The purpose of this study was to determine: 1) the extent to which an acute session of high-intensity interval training (HIIT) increases systemic inflammatory cytokines and chemokines, and 2) whether 2 weeks of HIIT training alters the inflammatory response. Eight recreationally active males (aged 22±2 years) performed 2 weeks of HIIT on a cycle ergometer (six HIIT sessions at 8–12 intervals; 60-second intervals, 75-second active rest) at a power output equivalent to 100% of their predetermined peak oxygen uptake (VO2max). Serum samples were collected during the first and sixth HIIT sessions at rest and immediately, 15, 30, and 45 minutes post-exercise. An acute session of HIIT induced significant increases in interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α, and monocyte chemotactic protein-1 compared with rest. The concentrations of interferon-γ, granulocyte macrophage-colony-stimulating factor, and IL-1β were unaltered with an acute session of HIIT Two weeks of training did not alter the inflammatory response to an acute bout of HIIT exercise. Maximal power achieved during a VO2max test significantly increased 4.6%, despite no improvements in VO2max after 2 weeks of HIIT. These data suggest that HIIT exercise induces a small inflammatory response in young, recreationally active men; however, 2 weeks of HIIT does not alter this response. PMID:24520199

  12. MODERN INSIGHTS INTO THE ROLE OF HEMORHEOLOGICAL DEVIATIONS AND FUNCTIONAL STATUS OF THE ENDOTHELIAL TISSUE IN THE PATHOGENESIS OF ACUTE INFLAMMATORY LUNG AND BRONCHIAL DISEASES AMONG CHILDREN

    Directory of Open Access Journals (Sweden)

    A.V. Mozhaev

    2007-01-01

    Full Text Available Disorders of the endothelial tissue and hemorheology function build up one of the pathogenic bases to form the acute inflammatory abnormality of the respiratory tract among children. The overview highlights the information on the role and disorders of the erythrocyte clumping and plasticity, blood viscosity and function of the endothelial tissue as a response to the acute respiratory infections among children.Key words: endothelial dysfunction, hemorheology, hemorheological deviations, acute respiratory infections, acute bronchopulmonary diseases, children.

  13. Effect of sympathetic nerve block on acute inflammatory pain and hyperalgesia

    DEFF Research Database (Denmark)

    Pedersen, J L; Rung, G W; Kehlet, H

    1997-01-01

    . The duration and quality of blocks were evaluated by the sympatogalvanic skin response and skin temperature. Bilateral heat injuries were produced on the medial surfaces of the calves with a 50 x 25 mm thermode (47 degrees C, 7 min) 45 min after the blocks. Pain intensity induced by heat, pain thresholds....... METHODS: The study was made as a randomized, single blinded investigation, in which the volunteers served as their own controls. A lumbar sympathetic nerve block and a contralateral placebo block were performed in 24 persons by injecting 10 ml bupivacaine (0.5%) and 10 ml saline, respectively...... acute inflammatory pain or hyperalgesia after a heat injury in human skin....

  14. Hyperalgesia in a human model of acute inflammatory pain: a methodological study

    DEFF Research Database (Denmark)

    Pedersen, J L; Kehlet, H

    1998-01-01

    sensitive to heat pain on their left side (P ... measurements themselves evoked hyperalgesia to heat and mechanical stimuli on the arm, but only to mechanical stimuli on the legs. including secondary hyperalgesia. Hyperalgesia evoked by the measurements was significantly less intense than that induced by injury. Habituation to the painful stimuli...... was demonstrated by significantly higher pain thresholds and lower pain responses on the second and third day of the study. The burn model is a sensitive psychophysical model of acute inflammatory pain, when cross-over designs and within-day comparisons are used, and the model is suitable for double-blind, placebo...

  15. Effects of four antiplatelet/statin combined strategies on immune and inflammatory responses in patients with acute myocardial infarction undergoing pharmacoinvasive strategy: Design and rationale of the B and T Types of Lymphocytes Evaluation in Acute Myocardial Infarction (BATTLE-AMI) study: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Fonseca, Francisco A H; Izar, Maria Cristina; Maugeri, Ieda M L; Berwanger, Otavio; Damiani, Lucas P; Pinto, Ibraim M; Szarf, Gilberto; França, Carolina N; Bianco, Henrique T; Moreira, Flavio T; Caixeta, Adriano; Alves, Claudia M R; Soriano Lopes, Aline; Klassen, Aline; Tavares, Marina F M; Fonseca, Henrique A; Carvalho, Antonio C C

    2017-12-19

    Early reperfusion of the occluded coronary artery during acute myocardial infarction is considered crucial for reduction of infarcted mass and recovery of ventricular function. Effective microcirculation and the balance between protective and harmful lymphocytes may have roles in reperfusion injury and may affect final ventricular remodeling. BATTLE-AMI is an open-label, randomized trial comparing the effects of four therapeutic strategies (rosuvastatin/ticagrelor, rosuvastatin/clopidogrel, simvastatin plus ezetimibe/ticagrelor, or simvastatin plus ezetimibe/clopidogrel) on infarcted mass and left ventricular ejection fraction (LVEF) (blinded endpoints) in patients with ST-segment elevation myocardial infarction submitted to fibrinolytic therapy before coronary angiogram (pharmacoinvasive strategy). All patients (n = 300, 75 per arm) will be followed up for six months. The effects of treatment on subsets of B and T lymphocytes will be determined by flow-cytometry/ELISPOT and will be correlated with the infarcted mass, LVEF, and microcirculation perfusion obtained by cardiac magnetic resonance imaging. The primary hypothesis is that the combined rosuvastatin/ticagrelor therapy will be superior to other therapies (particularly for the comparison with simvastatin plus ezetimibe/clopidogrel) for the achievement of better LVEF at 30 days (primary endpoint) and smaller infarcted mass (secondary endpoint) at 30 days and six months. The trial will also evaluate the improvement in the immune/inflammatory responses mediated by B and T lymphocytes. Omics field (metabolomics and proteomics) will help to understand these responses by molecular events. BATTLE-AMI is aimed to (1) evaluate the role of subsets of lymphocytes on microcirculation improvement and (2) show how the choice of statin/antiplatelet therapy may affect cardiac remodeling after acute myocardial infarction with ST elevation. ClinicalTrials.gov, NCT02428374 . Registered on 28 September 2014.

  16. Acute exercise does not induce an acute phase response (APR) in Standardbred trotters

    DEFF Research Database (Denmark)

    Kristensen, Lena; Buhl, Rikke; Nostell, Katarina

    2014-01-01

    The purpose of the study was to investigate whether acute strenuous exercise (1600- to 2500-m race) would elicit an acute phase response (APR) in Standardbred trotters. Blood levels of several inflammatory markers [serum amyloid A (SAA), haptoglobin, fibrinogen, white blood cell count (WBC......), and iron], muscle enzymes [creatinine kinase (CK) and aspartate transaminase (AST)], and hemoglobin were assessed in 58 Standardbred trotters before and after racing. Hemoglobin levels increased and iron levels decreased 12 to 14 h after racing and haptoglobin concentrations, white blood cell counts...

  17. Acrolein inhalation suppresses lipopolysaccharide-induced inflammatory cytokine production but does not affect acute airways neutrophilia.

    Science.gov (United States)

    Kasahara, David Itiro; Poynter, Matthew E; Othman, Ziryan; Hemenway, David; van der Vliet, Albert

    2008-07-01

    Acrolein is a reactive unsaturated aldehyde that is produced during endogenous oxidative processes and is a major bioactive component of environmental pollutants such as cigarette smoke. Because in vitro studies demonstrate that acrolein can inhibit neutrophil apoptosis, we evaluated the effects of in vivo acrolein exposure on acute lung inflammation induced by LPS. Male C57BL/6J mice received 300 microg/kg intratracheal LPS and were exposed to acrolein (5 parts per million, 6 h/day), either before or after LPS challenge. Exposure to acrolein either before or after LPS challenge did not significantly affect the overall extent of LPS-induced lung inflammation, or the duration of the inflammatory response, as observed from recovered lung lavage leukocytes and histology. However, exposure to acrolein after LPS instillation markedly diminished the LPS-induced production of several inflammatory cytokines, specifically TNF-alpha, IL-12, and the Th1 cytokine IFN-gamma, which was associated with reduction in NF-kappaB activation. Our data demonstrate that acrolein exposure suppresses LPS-induced Th1 cytokine responses without affecting acute neutrophilia. Disruption of cytokine signaling by acrolein may represent a mechanism by which smoking contributes to chronic disease in chronic obstructive pulmonary disease and asthma.

  18. Genetic and metabolic signals during acute enteric bacterial infection alter the microbiota and drive progression to chronic inflammatory disease

    Energy Technology Data Exchange (ETDEWEB)

    Kamdar, Karishma; Khakpour, Samira; Chen, Jingyu; Leone, Vanessa; Brulc, Jennifer; Mangatu, Thomas; Antonopoulos, Dionysios A.; Chang, Eugene B; Kahn, Stacy A.; Kirschner, Barbara S; Young, Glenn; DePaolo, R. William

    2016-01-13

    Chronic inflammatory disorders are thought to arise due to an interplay between predisposing host genetics and environmental factors. For example, the onset of inflammatory bowel disease is associated with enteric proteobacterial infection, yet the mechanistic basis for this association is unclear. We have shown previously that genetic defiency in TLR1 promotes acute enteric infection by the proteobacteria Yersinia enterocolitica. Examining that model further, we uncovered an altered cellular immune response that promotes the recruitment of neutrophils which in turn increases metabolism of the respiratory electron acceptor tetrathionate by Yersinia. These events drive permanent alterations in anti-commensal immunity, microbiota composition, and chronic inflammation, which persist long after Yersinia clearence. Deletion of the bacterial genes involved in tetrathionate respiration or treatment using targeted probiotics could prevent microbiota alterations and inflammation. Thus, acute infection can drive long term immune and microbiota alterations leading to chronic inflammatory disease in genetically predisposed individuals.

  19. Plasma inflammatory biomarkers response to aerobic versus ...

    African Journals Online (AJOL)

    contributes to the pathogenesis of atherosclerosis and cardiovascular disease. However, increase of inflammatory cytokines adversely affects quality of life, alteration in ventilatory and skeletal muscles functions. Moreover, exercise training has many beneficial effects in correction of the adverse effects of COPD. Objective: ...

  20. Acute inflammatory reaction in rats after intratracheal instillation of material collected from a nylon flocking plant.

    Science.gov (United States)

    Porter, D W; Castranova, V; Robinson, V A; Hubbs, A F; Mercer, R R; Scabilloni, J; Goldsmith, T; Schwegler-Berry, D; Battelli, L; Washko, R; Burkhart, J; Piacitelli, C; Whitmer, M; Jones, W

    1999-05-14

    fraction was much less active. Histological analysis of the lungs 1 d post-IT confirmed lung inflammation was occurring and tended to center around bronchioles. The results suggest that: (1) nylon flocking generates particles of respirable size that can interact with AM in the lung and can be detected in the lung 29 d after exposure, (2) the dust samples examined cause an inflammatory response, (3) water-extractable agent(s) from airborne dust contribute only minimally to the inflammatory response, and (4) the acute inflammatory response to these dusts is substantial when compared to other pathologic occupational dusts previously examined in our laboratory.

  1. CT appearance of acute inflammatory disease of the renal interstitium

    International Nuclear Information System (INIS)

    Gold, R.P.; McClennan, B.L.; Rottenberg, R.R.

    1983-01-01

    Today, infection remains the most common disease of the urinary tract and constitutes almost 75% of patient problems requiring urologic evaluation. There have been several major factors responsible for our better understanding of the nature and pathophysiology of urinary tract infection. One has been quantitated urine bacteriology and another, the discovery that a significant part of the apparently healthy adult female population has asymptomatic bacteriuria. Abnormal conditions such as neurogenic bladder, bladder malignancy, prolonged catheter drainage and reflux, altered host resistance, diabetes mellitus, and urinary tract obstruction, as well as pregnancy, may either predispose to or be implicated in the pathogenesis of urinary tract infection. There is a wide range of conditions that result in acute renal inflammation and those under discussion affect primarily the interstitium. This term refers to the connective tissue elements separating the tubules in the cortex and medulla. Hence, the interstitial nephritides are to be distinguished from the glomerulonephritides and fall into two general etiologic categories: infectious and noninfectious

  2. CT appearance of acute inflammatory disease of the renal interstitium

    Energy Technology Data Exchange (ETDEWEB)

    Gold, R.P. (New York Medical Coll., Valhalla); McClennan, B.L.; Rottenberg, R.R.

    1983-08-01

    Today, infection remains the most common disease of the urinary tract and constitutes almost 75% of patient problems requiring urologic evaluation. There have been several major factors responsible for our better understanding of the nature and pathophysiology of urinary tract infection. One has been quantitated urine bacteriology and another, the discovery that a significant part of the apparently healthy adult female population has asymptomatic bacteriuria. Abnormal conditions such as neurogenic bladder, bladder malignancy, prolonged catheter drainage and reflux, altered host resistance, diabetes mellitus, and urinary tract obstruction, as well as pregnancy, may either predispose to or be implicated in the pathogenesis of urinary tract infection. There is a wide range of conditions that result in acute renal inflammation and those under discussion affect primarily the interstitium. This term refers to the connective tissue elements separating the tubules in the cortex and medulla. Hence, the interstitial nephritides are to be distinguished from the glomerulonephritides and fall into two general etiologic categories: infectious and noninfectious.

  3. Anti-inflammatory Activity of Matricaria recutita L. against Acute and ...

    African Journals Online (AJOL)

    We investigated the effects of Matricaria recutita L. (MR) in acute and chronic inflammatory conditions. The anti-inflammatory activity of Matricaria recutita was studied against carrageenan induced hind paw, arachidonic acid, acetic acid and complete Freund's adjuvant (CFA)-induced arthritis in rats. The methanol extract of ...

  4. Helicobacter hepaticus Induces an Inflammatory Response in Primary Human Hepatocytes

    Science.gov (United States)

    Kleine, Moritz; Worbs, Tim; Schrem, Harald; Vondran, Florian W. R.; Kaltenborn, Alexander; Klempnauer, Jürgen; Förster, Reinhold; Josenhans, Christine; Suerbaum, Sebastian; Bektas, Hüseyin

    2014-01-01

    Helicobacter hepaticus can lead to chronic hepatitis and hepatocellular carcinoma in certain strains of mice. Until now the pathogenic role of Helicobacter species on human liver tissue is still not clarified though Helicobacter species identification in human liver cancer was successful in case controlled studies. Therefore we established an in vitro model to investigate the interaction of primary human hepatocytes (PHH) with Helicobacter hepaticus. Successful co-culturing of PHH with Helicobacter hepaticus was confirmed by visualization of motile bacteria by two-photon-microscopy. Isolated human monocytes were stimulated with PHH conditioned media. Changes in mRNA expression of acute phase cytokines and proteins in PHH and stimulated monocytes were determined by Real-time PCR. Furthermore, cytokines and proteins were analyzed in PHH culture supernatants by ELISA. Co-cultivation with Helicobacter hepaticus induced mRNA expression of Interleukin-1 beta (IL-1β), Tumor necrosis factor-alpha, Interleukin-8 (IL-8) and Monocyte chemotactic protein-1 (MCP-1) in PHH (pmedia (p<0.05). An increase of Cyclooxygenase-2 mRNA expression was observed, with a concomitant increase of prostaglandin E2 concentration in PHH supernatants at 24 and 48 h (p<0.05). In contrast, at day 7 of co-culture, no persistent elevation of cytokine mRNA could be detected. High expression of intercellular adhesion molecule-1 on PHH cell membranes after co-culture was shown by two-photon-microscopy and confirmed by flow-cytomety. Finally, expression of Cytochrome P450 3A4 and albumin mRNA were downregulated, indicating an impairment of hepatocyte synthesis function by Helicobacter hepaticus presence. This is the first in vitro model demonstrating a pathogenic effect of a Helicobacter spp. on human liver cells, resulting in an inflammatory response with increased synthesis of inflammatory mediators and consecutive monocyte activation. PMID:24932686

  5. Systemic inflammatory responses following welding inhalation challenge test

    Directory of Open Access Journals (Sweden)

    Paula Kauppi

    2015-01-01

    Conclusions: Exposure to MS and SS welding fume resulted in a mild systemic inflammatory response. The particle concentration from the breathing zones correlated with the measurements inside the welding face shields.

  6. The Biochemical Origin of Pain: The origin of all Pain is Inflammation and the Inflammatory Response. PART 2 of 3 –Inflammatory Profile of Pain Syndromes

    Science.gov (United States)

    2009-01-01

    Every pain syndrome has an inflammatory profile consisting of the inflammatory mediators that are present in the pain syndrome. The inflammatory profile may have variations from one person to another and may have variations in the same person at different times. The key to treatment of Pain Syndromes is an understanding of their inflammatory profile. Pain syndromes may be treated medically or surgically. The goal should be inhibition or suppression of production of the inflammatory mediators and inhibition, suppression or modulation of neuronal afferent and efferent (motor) transmission. A successful outcome is one that results in less inflammation and thus less pain. We hereby describe the inflammatory profile for several pain syndromes including arthritis, back pain, neck pain, fibromyalgia, interstitial cystitis, migraine, neuropathic pain, complex regional pain syndrome / reflex sympathetic dystrophy (CRPS/RSD), bursitis, shoulder pain and vulvodynia. These profiles are derived from basic science and clinical research performed in the past by numerous investigators and will be updated in the future by new technologies such as magnetic resonance spectroscopy. Our unifying theory or law of pain states: The origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain arise from inflammation and the inflammatory response. We are proposing

  7. Macrophage Expression of Inflammatory Genes in Response to EMCV Infection

    Directory of Open Access Journals (Sweden)

    Zachary R. Shaheen

    2015-08-01

    Full Text Available The expression and production of type 1 interferon is the classic cellular response to virus infection. In addition to this antiviral response, virus infection also stimulates the production of proinflammatory mediators. In this review, the pathways controlling the induction of inflammatory genes and the roles that these inflammatory mediators contribute to host defense against viral pathogens will be discussed. Specific focus will be on the role of the chemokine receptor CCR5, as a signaling receptor controlling the activation of pathways leading to virus-induced inflammatory gene expression.

  8. Isoliquiritigenin protects against sepsis-induced lung and liver injury by reducing inflammatory responses.

    Science.gov (United States)

    Chen, Xiong; Cai, Xueding; Le, Rongrong; Zhang, Man; Gu, Xuemei; Shen, Feixia; Hong, Guangliang; Chen, Zimiao

    2018-02-05

    Sepsis, one of the most fatal diseases worldwide, often leads to multiple organ failure, mainly due to uncontrolled inflammatory responses. Despite accumulating knowledge obtained in recent years, effective drugs to treat sepsis in the clinic are still urgently needed. Isoliquiritigenin (ISL), a chalcone compound, has been reported to exert anti-inflammatory properties. However, little is known about the effects of ISL on sepsis and its related complications. In this study, we investigated the potential protective effects of ISL on lipopolysaccharide (LPS)-induced injuries and identified the mechanisms underlying these effects. ISL inhibited inflammatory cytokine expression in mouse primary peritoneal macrophages (MPMs) exposed to LPS. In an acute lung injury (ALI) mouse model, ISL prevented LPS-induced structural damage and inflammatory cell infiltration. Additionally, pretreatment with ISL attenuated sepsis-induced lung and liver injury, accompanied by a reduction in inflammatory responses. Moreover, these protective effects were mediated by the nuclear factor kappa B (NF-κB) pathway-mediated inhibition of inflammatory responses in vitro and in vivo. Our study suggests that ISL may be a potential therapeutic agent for sepsis-induced injuries. Copyright © 2017. Published by Elsevier Inc.

  9. Pathological differences in acute inflammatory demyelinating diseases of the central nervous system.

    Science.gov (United States)

    Wegner, C

    2005-04-01

    This article reviews the different pathological and immunological features of MS, acute variants of MS and acute disseminated encephalomyelitis (ADEM). T-cell-mediated inflammatory reactions are involved in all acute inflammatory diseases of the central nervous system, but the diseases discussed also exhibit distinct immunopathological features. The perivascular infiltrate of T-cells and macrophages seen in ADEM resembles the pathological pattern found in experimental autoimmune encephalomyelitis. In addition, there is evidence that humoral mechanisms play a crucial role in some acute MS lesions, Devics syndrome and Marburgs syndrome. Analysis of acute MS lesions shows many different structural and immunological features, indicating that different mechanisms may be involved in lesion formation. Distinct subtypes of acute lesions exhibit either similarities with T-cell-mediated autoimmune encephalomyelitis or signs of primary oligodendrocyte damage.

  10. Pronounced inflammatory response to endotoxaemia during nighttime

    DEFF Research Database (Denmark)

    Alamili, Mahdi; Bendtzen, Klaus; Lykkesfeldt, Jens

    2014-01-01

    endotoxaemia model. DESIGN AND METHODS: A cross-over study, where 12 healthy young men received E. coli endotoxin (lipopolysaccharide, LPS) 0.3 ng/kg at 12 noon and, on another day, at 12 midnight. Blood samples were analysed for pro- and anti-inflammatory cytokines: tumour-necrosis factor (TNF)-alpha, soluble...... TNF receptors (sTNF-R)-1 and -2, interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, and IL-10 as well as YKL-40 and the oxidative stress markers malondialdehyde (MDA), ascorbic acid (AA) and dehydroascorbic acid (DHA) before and at 2, 4, 6 and 8 hours after LPS administration. RESULTS...

  11. A breakthrough in probiotics: Clostridium butyricum regulates gut homeostasis and anti-inflammatory response in inflammatory bowel disease.

    Science.gov (United States)

    Kanai, Takanori; Mikami, Yohei; Hayashi, Atsushi

    2015-09-01

    Intestinal immune homeostasis is regulated by gut microbiota, including beneficial and pathogenic microorganisms. Imbalance in gut bacterial constituents provokes host proinflammatory responses causing diseases such as inflammatory bowel disease (IBD). The development of next-generation sequencing technology allows the identification of microbiota alterations in IBD. Several studies have shown reduced diversity in the gut microbiota of patients with IBD. Advances in gnotobiotic technology have made possible analysis of the role of specific bacterial strains in immune cells in the intestine. Using these techniques, we have shown that Clostridium butyricum as a probiotic induces interleukin-10-producing macrophages in inflamed mucosa via the Toll-like receptor 2/myeloid differentiation primary response gene 88 pathway to prevent acute experimental colitis. In this review, we focus on the new approaches for the role of specific bacterial strains in immunological responses, as well as the potential of bacterial therapy for IBD treatments.

  12. Influence of dexamethasone and gamithromycin on the acute phase response in LPS-challenged calves

    OpenAIRE

    Plessers, Elke; Watteyn, Anneleen; Wyns, Heidi; Pardon, Bart; De Backer, Patrick; Croubels, Siska

    2012-01-01

    Introduction : Lipopolysaccharide (LPS) is a potent inducer of the bovine acute phase response and has been widely used in research to provoke acute inflammation. An intravenous challenge with LPS elicits the endogenous synthesis and release of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). These cytokines initiate fever and stimulate the hepatic production of acute phase proteins, such as Serum Amyloid A (SAA). Regarding the fact that immuno...

  13. Acute Inflammatory Demyelinating Polyneuropathy and a Unilateral Babinski/Plantar Reflex

    Directory of Open Access Journals (Sweden)

    Davide Cattano

    2008-01-01

    Full Text Available Acquired acute demyelinating peripheral polyneuropathy (AADP is a general classification of pathologies that could affect secondary the peripheral nervous system. They are characterized by an autoimmune process directed towards myelin. Clinically they are characterized by progressive weakness and mild sensory changes. Acute inflammatory demyelinating polyneuropathy often is referred to as Guillain-Barré syndrome (GBS. GBS is the major cause of acute nontraumatic paralysis in healthy people and it is caused by autoimmune response to viral agents (influenza, coxsackie, Epstein-Barr virus, or cytomegalovirus or bacterial infective organisms (Campylobacter jejuni, Mycoplasma pneumoniae. A detailed history, with symptoms of progressive usually bilateral weakness, hyporeflexia, with a typical demyelinating EMG pattern supports the diagnosis. Progressive affection of respiratory muscles and autonomic instability coupled with a protracted and unpredictable recovery normally results in the need for ICU management. We present a case report of a patient with a typical GBS presentation but with a unilateral upgoing plantar reflex (Babinski sign. A unifying diagnosis was made and based on a literature search in Pubmed appears to be the first described case of its kind.

  14. The patterns of toxicity and management of acute nonsteroidal anti-inflammatory drug (NSAID overdose

    Directory of Open Access Journals (Sweden)

    Hunter L

    2011-07-01

    Full Text Available Laura J Hunter, David M Wood, Paul I DarganClinical Toxicology, Guy’s and St Thomas’ NHS Foundation Trust, London, UKAbstract: The nonsteroidal anti-inflammatory drugs (NSAIDs are widely used for their analgesic, anti-inflammatory and antipyretic actions. They are commonly taken in overdose in many areas of the world. The majority of patients with acute NSAID overdose will remain asymptomatic or develop minor self-limiting gastrointestinal symptoms. However, serious clinical sequelae have been reported in patients with acute NSAID overdose and these include convulsions, metabolic acidosis, coma and acute renal failure. There appear to be some differences between the NSAIDs in terms of the relative risk of these complications; in particular mefenamic acid is most commonly associated with convulsions. The management of these serious clinical features is largely supportive and there are no specific antidotes for acute NSAID toxicity.Keywords: nonsteroidal anti-inflammatory drugs (NSAID, ibuprofen, toxicity, poisoning, overdose, management

  15. Senescence-associated inflammatory responses: aging and cancer perspectives.

    Science.gov (United States)

    Lasry, Audrey; Ben-Neriah, Yinon

    2015-04-01

    Senescent cells, albeit not proliferating, are metabolically and transcriptionally active, thereby capable of affecting their microenvironment, notably via the production of inflammatory mediators. These mediators maintain and propagate the senescence process to neighboring cells, and then recruit immune cells for clearing senescent cells. Among the inflammatory cues are molecules with pronounced tumor-controlling properties, both growth and invasion factors and inhibitory factors, working directly or via recruited immune cells. These senescence-inflammatory effects also prevail within tumors, mediated by the senescent tumor cells and the senescent tumor stroma. Here, we review the course and impact of senescence-associated inflammatory responses in aging and cancer. We propose that controlling senescence-associated inflammation by targeting specific inflammatory mediators may have a beneficial therapeutic effect in treatment of cancer and aging-related diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. An NF-κB-microRNA regulatory network tunes macrophage inflammatory responses.

    Science.gov (United States)

    Mann, Mati; Mehta, Arnav; Zhao, Jimmy L; Lee, Kevin; Marinov, Georgi K; Garcia-Flores, Yvette; Baltimore, David

    2017-10-11

    The innate inflammatory response must be tightly regulated to ensure effective immune protection. NF-κB is a key mediator of the inflammatory response, and its dysregulation has been associated with immune-related malignancies. Here, we describe a miRNA-based regulatory network that enables precise NF-κB activity in mouse macrophages. Elevated miR-155 expression potentiates NF-κB activity in miR-146a-deficient mice, leading to both an overactive acute inflammatory response and chronic inflammation. Enforced miR-155 expression overrides miR-146a-mediated repression of NF-κB activation, thus emphasizing the dominant function of miR-155 in promoting inflammation. Moreover, miR-155-deficient macrophages exhibit a suboptimal inflammatory response when exposed to low levels of inflammatory stimuli. Importantly, we demonstrate a temporal asymmetry between miR-155 and miR-146a expression during macrophage activation, which creates a combined positive and negative feedback network controlling NF-κB activity. This miRNA-based regulatory network enables a robust yet time-limited inflammatory response essential for functional immunity.MicroRNAs (miR) are important regulators of gene transcription, with miR-155 and miR-146a both implicated in macrophage activation. Here the authors show that NF-κB signalling, miR-155 and miR-146a form a complex network of cross-regulations to control gene transcription in macrophages for modulating inflammatory responses.

  17. The immune response to Prevotella bacteria in chronic inflammatory disease

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura

    2017-01-01

    The microbiota plays a central role in human health and disease by shaping immune development, immune responses and metabolism, and by protecting from invading pathogens. Technical advances that allow comprehensive characterization of microbial communities by genetic sequencing have sparked......-8, IL-6 and CCL20, which can promote mucosal Th17 immune responses and neutrophil recruitment. Prevotella-mediated mucosal inflammation leads to systemic dissemination of inflammatory mediators, bacteria and bacterial products, which in turn may affect systemic disease outcomes. Studies in mice...... support a causal role of Prevotella as colonization experiments promote clinical and inflammatory features of human disease. When compared with strict commensal bacteria, Prevotella exhibit increased inflammatory properties, as demonstrated by augmented release of inflammatory mediators from immune cells...

  18. The role of multiple negative social relationships in inflammatory cytokine responses to a laboratory stressor

    Directory of Open Access Journals (Sweden)

    Sunmi Song

    2015-06-01

    Full Text Available The present study examined the unique impact of perceived negativity in multiple social relationships on endocrine and inflammatory responses to a laboratory stressor. Via hierarchical cluster analysis, those who reported negative social exchanges across relationships with a romantic partner, family, and their closest friend had higher mean IL-6 across time and a greater increase in TNF-α from 15 min to 75 min post stress. Those who reported negative social exchanges across relationships with roommates, family, and their closest friend showed greater IL-6 responses to stress. Differences in mean IL-6 were accounted for by either depressed mood or hostility, whereas differences in the cytokine stress responses remained significant after controlling for those factors. Overall, this research provides preliminary evidence to suggest that having multiple negative relationships may exacerbate acute inflammatory responses to a laboratory stressor independent of hostility and depressed mood.

  19. Circulating soluble endoglin modifies the inflammatory response in mice.

    Science.gov (United States)

    Ruiz-Remolina, Laura; Ollauri-Ibáñez, Claudia; Pérez-Roque, Lucía; Núñez-Gómez, Elena; Pérez-Barriocanal, Fernando; López-Novoa, José Miguel; Pericacho, Miguel; Rodríguez-Barbero, Alicia

    2017-01-01

    Inflammation is associated with every health condition, and is an important component of many pathologies such as cardiovascular diseases. Circulating levels of soluble endoglin have been shown to be higher in the serum of patients with cardiovascular diseases with a significant inflammatory component. The aim of this study was to evaluate the implication of circulating soluble endoglin in the inflammatory response. For this purpose, a transgenic mouse expressing human soluble endoglin (sEng+) was employed, and three different inflammatory approaches were used to mimic inflammatory conditions in different tissues. This study shows that control sEng+ mice have a normal inflammatory state. The lung and kidney injury induced by the inflammatory agents was reduced in sEng+ mice, especially the intra-alveolar and kidney infiltrates, suggesting a possible reduction in inflammation induced by soluble endoglin. To deepen into this possible effect, the leukocyte number in the bronchoalveolar lavage and air pouch lavage was evaluated and a significant reduction of neutrophil infiltration in LPS-treated lungs and ischemic kidneys from sEng+ with respect to WT mice was observed. Additionally, the mechanisms through which soluble endoglin prevents inflammation were studied. We found that in sEng+ animals the increment of proinflammatory cytokines, TNFα, IL1β and IL6, induced by the inflammatory stimulus was reduced. Soluble endoglin also prevents the augmented adhesion molecules, ICAM, VCAM and E-selectin induced by the inflammatory stimulus. In addition, vascular permeability increased by inflammatory agents was also reduced by soluble endoglin. These results suggest that soluble endoglin modulates inflammatory-related diseases and open new perspectives leading to the development of novel and targeted approaches for the prevention and treatment of cardiovascular diseases.

  20. Inflammatory response to mental stress and mental stress induced myocardial ischemia.

    Science.gov (United States)

    Hammadah, Muhammad; Sullivan, Samaah; Pearce, Brad; Al Mheid, Ibhar; Wilmot, Kobina; Ramadan, Ronnie; Tahhan, Ayman Samman; O'Neal, Wesley T; Obideen, Malik; Alkhoder, Ayman; Abdelhadi, Naser; Mohamed Kelli, Heval; Ghafeer, Mohamad Mazen; Pimple, Pratik; Sandesara, Pratik; Shah, Amit J; Hosny, Kareem Mohammed; Ward, Laura; Ko, Yi-An; Sun, Yan V; Weng, Lei; Kutner, Michael; Bremner, J Douglas; Sheps, David S; Esteves, Fabio; Raggi, Paolo; Vaccarino, Viola; Quyyumi, Arshed A

    2018-02-01

    Mental stress-induced myocardial ischemia (MSIMI) is associated with increased risk of adverse cardiovascular outcomes, yet the underlying mechanisms are not well understood. We measured the inflammatory response to acute laboratory mental stress in patients with coronary artery disease (CAD) and its association with MSIMI. We hypothesized that patients with MSIMI would have a higher inflammatory response to mental stress in comparison to those without ischemia. Patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging during mental stress testing using a public speaking stressor. MSIMI was determined as impaired myocardial perfusion using a 17-segment model. Inflammatory markers including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), matrix metallopeptidase 9 (MMP-9) and high-sensitivity C reactive protein (hsCRP) were measured at rest and 90 min after mental stress. Results were validated in an independent sample of 228 post-myocardial infarction patients. Of 607 patients analyzed in this study, (mean age 63 ± 9 years, 76% male), 99 (16.3%) developed MSIMI. Mental stress resulted in a significant increase in IL-6, MCP-1, and MMP-9 (all p mental stress were significantly associated with MSIMI. Results in the replication sample were similar. Mental stress is associated with acute increases in several inflammatory markers. However, neither the baseline inflammatory status nor the magnitude of the inflammatory response to mental stress over 90 min were significantly associated with MSIMI. Copyright © 2017. Published by Elsevier Inc.

  1. [Investigations on the acute, carrageenan-induced inflammatory reaction and pharmacology of orally administered sodium salicylate in turkeys].

    Science.gov (United States)

    Cramer, Kerstin; Schmidt, Volker; Richter, Andreas; Fuhrmann, Herbert; Abraham, Getu; Krautwald-Junghanns, Maria-Elisabeth

    2015-01-01

    The complex mechanisms of acute inflammation have been subject to veterinary investigations since a long time. However, knowledge on the role of specific inflammatory mediators, as well as pharmacokinetics (PK) and -dynamics (PD) of non-steroidal anti-inflammatory drugs (NSAID) in birds is limited. The objective of this work therefore was to establish a modified tissue cage-model to investigate the acute, carrageenan-mediated inflammatory response, as well as plasma and exudate-kinetics and the antiphlogistic effect of orally administered sodium salicylate on the elicited inflammatory reaction in turkeys. Within the class Aves, comparable studies have so far only been published in chicken. Following bilateral subcutaneous implantation of carrageenan-treated synthetic sponges in the lateral thoracic region, sodium salicylate was administered orally at a dose of 50 mg/kg body weight (BW; therapy group) twice daily on three consecutive days, while a control group received drinking water as a placebo (n = 24 per group). Combined PK and PD of sodium salicylate were evaluated on the basis of salicylate- and prostaglandin (PG) E2-plasma- and -exudate-concentrations, exudate volumes, as well as leukocyte exudate counts. Sodium salicylate was readily absorbed from the gastrointestinal tract and accumulated in the inflammatory exudate. At 4, 6, and 10 h after first application, sodium salicylate significantly reduced PG E2-concentrations in the inflammatory exudate when compared to the control group, whereas leukocyte exudate counts increased over time in both study groups, unaffected by sodium salicylate The described modified tissue cage-model can be beneficial for further research on the pathophysiology of avian inflammatory processes and the investigation of the combined pharmacodynamics and -kinetics of drugs in birds of adequate size.

  2. Acute pelvic inflammatory disease: pictorial essay focused on computed tomography and magnetic resonance imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Febronio, Eduardo Miguel; Rosas, George de Queiroz; D' Ippolito, Giuseppe, E-mail: giuseppe_dr@uol.com.br [Department of Imaging Diagnosis, Escola Paulista de Medicina - Universidade Federal de Sao Paulo (EPMUnifesp), Sao Paulo, SP (Brazil)

    2012-11-15

    The present study was aimed at describing key computed tomography and magnetic resonance imaging findings in patients with acute abdominal pain derived from pelvic inflammatory disease. Two radiologists consensually selected and analyzed computed tomography and magnetic resonance imaging studies performed between January 2010 and December 2011 in patients with proven pelvic inflammatory disease leading to presentation of acute abdomen. Main findings included presence of intracavitary fluid collections, anomalous enhancement of the pelvic excavation and densification of adnexal fat planes. Pelvic inflammatory disease is one of the leading causes of abdominal pain in women of childbearing age and it has been increasingly been diagnosed by means of computed tomography and magnetic resonance imaging supplementing the role of ultrasonography. It is crucial that radiologists become familiar with the main sectional imaging findings in the diagnosis of this common cause of acute abdomen (author)

  3. Acute toxicity studies, anti-inflammatory and analgesic activities of ...

    African Journals Online (AJOL)

    Methanolic extracts of the stem bark of Enantia chlorantha and Nauclea latifolia were investigated in rats and mice for anti-inflammatory and analgesic activities. The activities of the extracts were tested on egg white-induced oedema, acetic acid-induced writhing and hot plate models. Methanolic extract of Nauclea latifolia ...

  4. Relevance of PDT-induced inflammatory response for the outcome of photodynamic therapy

    Science.gov (United States)

    Korbelik, Mladen; Cecic, Ivana; Sun, Jinghai

    2001-07-01

    The treatment of solid cancerous lesions by photodynamic therapy (PDT) elicits an acute host reaction primarily manifested as a strong, rapidly developing inflammatory response. It is becoming increasingly clear that the destructive impact of the inflammatory process is directly responsible for the so-called indirect damage in PDT-treated tumors. The loss of vascular homeostasis followed by massive damage to vascular and perivascular regions in PDT- treated tumors and the ensuing tumor antigen-specific immunity, are direct consequences of critical initiating events including the action of complement, activation of poly(ADP-ribose)polymerase (PARP) and ischemia/reperfusion insult, and the associated cascades of tissue-destructive responses. Hence, the effectiveness of PDT as an anti- cancer modality is largely owed to the fact that it instigates a comprehensive engagement of powerful innate host defense mechanisms.

  5. Kaempferol, a dietary flavonoid, ameliorates acute inflammatory and nociceptive symptoms in gastritis, pancreatitis, and abdominal pain.

    Science.gov (United States)

    Kim, Shi Hyoung; Park, Jae Gwang; Sung, Gi-Ho; Yang, Sungjae; Yang, Woo Seok; Kim, Eunji; Kim, Jun Ho; Ha, Van Thai; Kim, Han Gyung; Yi, Young-Su; Kim, Ji Hye; Baek, Kwang-Soo; Sung, Nak Yoon; Lee, Mi-nam; Kim, Jong-Hoon; Cho, Jae Youl

    2015-07-01

    Kaempferol (KF) is the most abundant polyphenol in tea, fruits, vegetables, and beans. However, little is known about its in vivo anti-inflammatory efficacy and mechanisms of action. To study these, several acute mouse inflammatory and nociceptive models, including gastritis, pancreatitis, and abdominal pain were employed. Kaempferol was shown to attenuate the expansion of inflammatory lesions seen in ethanol (EtOH)/HCl- and aspirin-induced gastritis, LPS/caerulein (CA) triggered pancreatitis, and acetic acid-induced writhing. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Syk-Mediated Suppression of Inflammatory Responses by Cordyceps bassiana.

    Science.gov (United States)

    Yang, Woo Seok; Nam, Gyeong Sug; Kim, Mi-Yeon; Cho, Jae Youl

    2017-01-01

    The fruit body of artificially cultivated Cordyceps bassiana has been reported to exhibit anti-inflammatory and anticancer activities. Although it has been suggested that the fruit body has neutraceutic and pharmaceutic biomaterial potential, the exact anti-inflammatory molecular mechanism has not been fully elucidated. In this study, we demonstrated the immunopharmacologic activity of Cordyceps bassiana under in vitro conditions and investigated its anti-inflammatory mechanism. Water extract (Cm-WE) of the fruit body of artificially cultivated Cordyceps bassiana without polysaccharide fractions reduced the expression of the proinflammatory genes cyclooxygenase (COX)-2, interleukin (IL)-12, and inducible nitric oxide synthase (iNOS) and promoted the expression of the anti-inflammatory gene IL-10 in lipopolysaccharide (LPS)-treated RAW264.7 cells. In addition, this fraction suppressed proliferation and interferon (IFN)-[Formula: see text] production in splenic T lymphocytes. Cm-WE blocked the activation of nuclear factor (NF)-[Formula: see text]B and activator protein (AP)-1 and their upstream inflammatory signaling cascades, including Syk, MEK, and JNK. Using kinase assays, Syk was identified as the target enzyme most strongly inhibited by Cm-WE. These results strongly suggest that Cm-WE suppresses inflammatory responses by inhibiting Syk kinase activity, with potential implications for novel neutraceutic and pharmaceutic biomaterials.

  7. Human immunodeficiency virus seroconversion presenting with acute inflammatory demyelinating polyneuropathy: a case report

    Directory of Open Access Journals (Sweden)

    Sloan Derek J

    2008-12-01

    Full Text Available Abstract Introduction Acute Human Immunodeficiency Virus infection is associated with a range of neurological conditions. Guillain-Barré syndrome is a rare presentation; acute inflammatory demyelinating polyneuropathy is the commonest form of Guillain-Barré syndrome. Acute inflammatory demyelinating polyneuropathy has occasionally been reported in acute Immunodeficiency Virus infection but little data exists on frequency, management and outcome. Case presentation We describe an episode of Guillain-Barré syndrome presenting as acute inflammatory demyelinating polyneuropathy in a 30-year-old man testing positive for Immunodeficiency Virus, probably during acute seroconversion. Clinical suspicion was confirmed by cerebrospinal fluid analysis and nerve conduction studies. Rapid clinical deterioration prompted intravenous immunoglobulin therapy and early commencement of highly active anti-retroviral therapy. All symptoms resolved within nine weeks. Conclusion Unusual neurological presentations in previously fit patients are an appropriate indication for Immunodeficiency-Virus testing. Highly active anti-retroviral therapy with adequate penetration of the central nervous system should be considered as an early intervention, alongside conventional therapies such as intravenous immunoglobulin.

  8. Nonsteroidal anti-inflammatory drugs may affect cytokine response and benefit healing of combat-related extremity wounds.

    Science.gov (United States)

    Lisboa, Felipe A; Bradley, Matthew J; Hueman, Matthew T; Schobel, Seth A; Gaucher, Beverly J; Styrmisdottir, Edda L; Potter, Benjamin K; Forsberg, Jonathan A; Elster, Eric A

    2017-04-01

    After adequate operative debridement and antimicrobial therapies, combat-related extremity wounds that either heal or fail are both associated with a distinct inflammatory response. Short-term use of nonsteroidal anti-inflammatory drugs in postoperative pain management may affect this response and, by consequence, the healing potential of these wounds. We investigated whether patients treated with nonsteroidal anti-inflammatory drugs had a distinct inflammatory response; different rates of critical colonization, defined as >10 5 colony forming units on quantitative bacteriology; and healing potential. We retrospectively reviewed the records of 73 patients with combat-related extremity wounds. Patients were separated into 2 groups: those who received nonsteroidal anti-inflammatory drugs during the debridement period (nonsteroidal anti-inflammatory drugs group, N = 17) and those who did not (control group; N = 56). Serum and wound tissue samples collected during each operative debridement were measured for 32 known cytokines and tested for quantitative bacteriology, respectively. We compared cytokine concentrations between groups and then designed a logistic regression model to identify variables associated with successful wound healing, while controlling for known confounders. Despite similar demographics and wound characteristics, the nonsteroidal anti-inflammatory drugs group had significant lesser concentrations of inflammatory cytokines, interleukin-2, interleukin-6, interleukin-8, and monocyte chemoattractant protein-1. On multivariate analysis, nonsteroidal anti-inflammatory drug treatment emerged as a predictor of successful wound healing after controlling for known confounders such as wound size, tobacco use, Acute Physiology and Chronic Health Evaluation II score, and critical colonization. Treatment with nonsteroidal anti-inflammatory drugs for postoperative pain management after major combat-related extremity trauma is associated with lesser

  9. Involvement of the melanocortin-1 receptor in acute pain and pain of inflammatory but not neuropathic origin.

    Directory of Open Access Journals (Sweden)

    Ada Delaney

    2010-09-01

    Full Text Available Response to painful stimuli is susceptible to genetic variation. Numerous loci have been identified which contribute to this variation, one of which, MC1R, is better known as a gene involved in mammalian hair colour. MC1R is a G protein-coupled receptor expressed in melanocytes and elsewhere and mice lacking MC1R have yellow hair, whilst humans with variant MC1R protein have red hair. Previous work has found differences in acute pain perception, and response to analgesia in mice and humans with mutations or variants in MC1R.We have tested responses to noxious and non-noxious stimuli in mutant mice which lack MC1R, or which overexpress an endogenous antagonist of the receptor, as well as controls. We have also examined the response of these mice to inflammatory pain, assessing the hyperalgesia and allodynia associated with persistent inflammation, and their response to neuropathic pain. Finally we tested by a paired preference paradigm their aversion to oral administration of capsaicin, which activates the noxious heat receptor TRPV1. Female mice lacking MC1R showed increased tolerance to noxious heat and no alteration in their response to non-noxious mechanical stimuli. MC1R mutant females, and females overexpressing the endogenous MC1R antagonist, agouti signalling protein, had a reduced formalin-induced inflammatory pain response, and a delayed development of inflammation-induced hyperalgesia and allodynia. In addition they had a decreased aversion to capsaicin at moderate concentrations. Male mutant mice showed no difference from their respective controls. Mice of either sex did not show any effect of mutant genotype on neuropathic pain.We demonstrate a sex-specific role for MC1R in acute noxious thermal responses and pain of inflammatory origin.

  10. Incidence of systemic inflammatory response syndrome after endovascular aortic repair

    DEFF Research Database (Denmark)

    De La Motte, L; Vogt, K; Jensen, Leif Panduro

    2011-01-01

    AIM: The aim of this study was to estimate the incidence of the post-implantation syndrome/systemic inflammatory response syndrome (SIRS) after endovascular aortic repair. METHODS: All patients, undergoing elective primary endovascular repair of an asymptomatic infrarenal abdominal aortic aneurysm...

  11. Investigation of inflammatory markers in horses with acute abdominal pain

    DEFF Research Database (Denmark)

    Pihl, Tina Holberg; Kjelgaard-Hansen, Mads; Andersen, Pia Haubro

    Background The use of acute phase proteins as objective markers of underlying pathology may facilitate the decision-making regarding diagnosis, treatment and estimation of prognosis of colic horses in a referral hospital. Evaluation of acute phase proteins in both serum and peritoneal fluid...... 19 healthy control horses. SAA and haptoglobin were measured in both serum and PF. Colic cases were classified according to diagnosis, treatment and outcome based on the clinical records. Protein concentrations were compared between groups with student´s t-test and ANOVA. Results Colic horses had...... and haptoglobin can be measured in equine peritoneal fluid similar to measurements in serum. The peritoneal fluid concentrations are more indicative of diagnosis, treatment necessary and outcome than the serum concentrations. Potential relevance Evaluation of SAA and haptoglobin in serum and peritoneal fluid...

  12. Titanium surface hydrophilicity modulates the human macrophage inflammatory cytokine response.

    Science.gov (United States)

    Alfarsi, Mohammed A; Hamlet, Stephen M; Ivanovski, Saso

    2014-01-01

    Increased titanium surface hydrophilicity has been shown to accelerate dental implant osseointegration. Macrophages are important in the early inflammatory response to surgical implant placement and influence the subsequent healing response. This study investigated the modulatory effect of a hydrophilic titanium surface on the inflammatory cytokine expression profile in a human macrophage cell line (THP-1). Genes for 84 cytokines, chemokines, and their receptors were analyzed following exposure to (1) polished (SMO), (2) micro-rough sand blasted, acid etched (SLA), and (3) hydrophilic-modified SLA (modSLA) titanium surfaces for 1 and 3 days. By day 3, the SLA surface elicited a pro-inflammatory response compared to the SMO surface with statistically significant up-regulation of 16 genes [Tumor necrosis factor (TNF) Interleukin (IL)-1β, Chemokine (C-C motif) ligand (CCL)-1, 2, 3, 4, 18, 19, and 20, Chemokine (C-X-C motif) ligand (CXCL)-1, 5, 8 and 12, Chemokine (C-C motif) receptor (CCR)-7, Lymphotoxin-beta (LTB), and Leukotriene B4 receptor (LTB4R)]. This effect was countered by the modSLA surface, which down-regulated the expression of 10 genes (TNF, IL-1α and β, CCL-1, 3, 19 and 20, CXCL-1 and 8, and IL-1 receptor type 1), while two were up-regulated (osteopontin and CCR5) compared to the SLA surface. These cytokine gene expression changes were confirmed by decreased levels of corresponding protein secretion in response to modSLA compared to SLA. These results show that a hydrophilic titanium surface can modulate human macrophage pro-inflammatory cytokine gene expression and protein secretion. An attenuated pro-inflammatory response may be an important molecular mechanism for faster and/or improved wound healing. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

  13. The role of genital chlamydial infection in acute pelvic inflammatory ...

    African Journals Online (AJOL)

    The result showed that 11.1 per cent of women with acute PID were infected with Chlamydia trachomatis as compared to 4.3 per cent in the control group (odds ratio 2.75: 95% confidence interval (CI), 0.7-11.7). Neiserria gonorrhoeae was not detected in either of the two groups. Trichomoniasis (10% in PID cases and no ...

  14. Role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P

    1995-01-01

    The role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the pathogenesis of acute lung injury in rats after intrapulmonary deposition of IgG immune complexes or intratracheal administration of LPS has been assessed. Critical to these studies was the cloning and functional expression...

  15. How to differentiate acute pelvic inflammatory disease from acute appendicitis ? A decision tree based on CT findings.

    Science.gov (United States)

    El Hentour, Kim; Millet, Ingrid; Pages-Bouic, Emmanuelle; Curros-Doyon, Fernanda; Molinari, Nicolas; Taourel, Patrice

    2018-02-01

    To construct a decision tree based on CT findings to differentiate acute pelvic inflammatory disease (PID) from acute appendicitis (AA) in women with lower abdominal pain and inflammatory syndrome. This retrospective study was approved by our institutional review board and informed consent was waived. Contrast-enhanced CT studies of 109 women with acute PID and 218 age-matched women with AA were retrospectively and independently reviewed by two radiologists to identify CT findings predictive of PID or AA. Surgical and laboratory data were used for the PID and AA reference standard. Appropriate tests were performed to compare PID and AA and a CT decision tree using the classification and regression tree (CART) algorithm was generated. The median patient age was 28 years (interquartile range, 22-39 years). According to the decision tree, an appendiceal diameter ≥ 7 mm was the most discriminating criterion for differentiating acute PID and AA, followed by a left tubal diameter ≥ 10 mm, with a global accuracy of 98.2 % (95 % CI: 96-99.4). Appendiceal diameter and left tubal thickening are the most discriminating CT criteria for differentiating acute PID from AA. • Appendiceal diameter and marked left tubal thickening allow differentiating PID from AA. • PID should be considered if appendiceal diameter is < 7 mm. • Marked left tubal diameter indicates PID rather than AA when enlarged appendix. • No pathological CT findings were identified in 5 % of PID patients.

  16. How to differentiate acute pelvic inflammatory disease from acute appendicitis? A decision tree based on CT findings

    International Nuclear Information System (INIS)

    El Hentour, Kim; Millet, Ingrid; Pages-Bouic, Emmanuelle; Curros-Doyon, Fernanda; Taourel, Patrice; Molinari, Nicolas

    2018-01-01

    To construct a decision tree based on CT findings to differentiate acute pelvic inflammatory disease (PID) from acute appendicitis (AA) in women with lower abdominal pain and inflammatory syndrome. This retrospective study was approved by our institutional review board and informed consent was waived. Contrast-enhanced CT studies of 109 women with acute PID and 218 age-matched women with AA were retrospectively and independently reviewed by two radiologists to identify CT findings predictive of PID or AA. Surgical and laboratory data were used for the PID and AA reference standard. Appropriate tests were performed to compare PID and AA and a CT decision tree using the classification and regression tree (CART) algorithm was generated. The median patient age was 28 years (interquartile range, 22-39 years). According to the decision tree, an appendiceal diameter ≥ 7 mm was the most discriminating criterion for differentiating acute PID and AA, followed by a left tubal diameter ≥ 10 mm, with a global accuracy of 98.2 % (95 % CI: 96-99.4). Appendiceal diameter and left tubal thickening are the most discriminating CT criteria for differentiating acute PID from AA. (orig.)

  17. Assessment of anti-inflammatory potential of Sesbania bispinosa Linn. leaf extracts and fractions by acute and

    Directory of Open Access Journals (Sweden)

    Ganesh D. Boddawar

    2016-09-01

    Conclusion: The results of the present study suggest that leaves of S. bispinosa possess significant level of anti-inflammatory activity and ethyl acetate fraction may be further explored as an anti-inflammatory remedy as it was found to possess higher anti-inflammatory activity among all extracts and fractions as demonstrated in both acute and chronic models.

  18. The octapetide NAP alleviates intestinal and extra-intestinal anti-inflammatory sequelae of acute experimental colitis.

    Science.gov (United States)

    Heimesaat, Markus M; Giladi, Eliezer; Kühl, Anja A; Bereswill, Stefan; Gozes, Illana

    2018-03-01

    The octapeptide NAP has been shown to exert neuroprotective properties and reduce neuro-inflammatory responses. The aim of the present study was to investigate if NAP provides anti-inflammatory effects in acute murine colitis. To address this, C57BL/6 j mice were challenged with 3.5% dextran sulfate sodium from day 0 until day 6 to induce colitis, either treated intraperitoneally with NAP or placebo (NaCl 0.9%) from day 1 until day 6 post-induction (p.i.) and subjected to in depth macroscopic, microscopic and immunological evaluations. Whereas NAP application did not alleviate macroscopic (i.e. clinical) sequelae of colitis, lower numbers of apoptotic, but higher counts of proliferating/regenerating colonic epithelial cells could be observed in NAP as compared to placebo treated mice at day 7 p.i. Furthermore, lower numbers of adaptive immune cells such as T lymphocytes and regulatory T cells were abundant in the colonic mucosa and lamina propria upon NAP versus placebo treatment that were accompanied by less colonic secretion of pro-inflammatory mediators including IFN-γ and nitric oxide at day 7 p.i. In mesenteric lymph nodes, pro-inflammatory IFN-γ, TNF and IL-6 concentrations were increased in placebo, but not NAP treated mice at day 7 p.i., whereas interestingly, elevated anti-inflammatory IL-10 levels could be observed in NAP treated mice only. The assessed anti-inflammatory properties of NAP were not restricted to the intestinal tract, given that in extra-intestinal compartments such as the kidneys, IFN-γ levels increased in placebo, but not NAP treated mice upon colitis induction. NAP induced effects were accompanied by distinct changes in intestinal microbiota composition, given that colonic luminal loads of bifidobacteria, regarded as anti-inflammatory, "health-promoting" commensal species, were two orders of magnitude higher in NAP as compared to placebo treated mice and even naive controls. In conclusion, NAP alleviates intestinal and extra

  19. The effects of acute and chronic exercise on inflammatory markers in children and adults with a chronic inflammatory disease: a systematic review

    NARCIS (Netherlands)

    Ploeger, Hilde E.; Takken, Tim; de Greef, Mathieu H. G.; Timmons, Brian W.

    2009-01-01

    Chronic inflammatory diseases strike millions of people all over the world, and exercise is often prescribed for these patients to improve overall fitness and quality of life. In healthy individuals, acute and chronic exercise is known to alter inflammatory markers; however, less is known about

  20. The effects of acute and chronic exercise on inflammatory markers in children and adults with a chronic inflammatory disease : a systematic review

    NARCIS (Netherlands)

    Ploeger, Hilde E.; Takken, Tim; de Greef, Mathieu H. G.; Timmons, Brian W.

    2009-01-01

    Background: Chronic inflammatory diseases strike millions of people all over the world, and exercise is often prescribed for these patients to improve overall fitness and quality of life. In healthy individuals, acute and chronic exercise is known to alter inflammatory markers; however, less is

  1. The effect of acute ophiobolin A treatment on HO-mediated inflammatory processes.

    Science.gov (United States)

    Pósa, Anikó; Szabó, Renáta; Szalai, Zita; Kupai, Krisztina; Deim, Zoltán; Murlasits, Zsolt; Bencsik, Ottó; Szekeres, András; Vágvölgyi, Csaba; Balogh, László; Juhász, Béla; Szilvássy, Zoltán; Varga, Csaba

    2017-06-01

    Many microbial and plant-derived metabolites contribute to the production of inflammatory mediators and the expression of pro-inflammatory molecules. Ophiobolin A (OPA) is a fungal secondary metabolite produced by Bipolaris species. The aim of our study was to examine the acute effects of this compound on inflammatory processes. Male Wistar rats were treated with 5% ethanol, 0.01 mg/kg OPA, 0.1 mg/kg OPA and 1.0 mg/kg OPA per os. After 24 h of the administrations, inflammatory mediators such as interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) enzyme as well as heme oxygenase (HO) activity were measured in both plasma and cardiac tissue, along with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). We found that OPA caused a significant elevation in the concentrations of IL-6 and TNF-α, increased MPO activity and decreased HO enzyme activity in the plasma. While OPA induces inflammation in the plasma, it did not change the level of inflammatory mediators in the cardiac tissue and the concentrations of serum ALT and AST. Our findings indicate that rapid release of inflammatory mediators by OPA promotes systemic inflammation. However, this acute OPA treatment does not show toxic effects on the cardiac tissue and the concentrations of liver enzymes.

  2. Risk of acute pancreatitis in patients with cronic inflammatory bowel disease

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Højgaard; Fonager, Kirsten; Sørensen, Henrik Toft

    1999-01-01

    BACKGROUND: There are few epidemiologic data about the risk of acute pancreatitis in chronic inflammatory bowel diseases; we therefore wanted to estimate the risk of a first episode of acute pancreatitis in patients with Crohn's disease and ulcerative colitis in the total Danish population. METHODS......: The study included all patients discharged from Danish hospitals with a diagnosis of Crohn's disease or ulcerative colitis registered in the Danish National Registry of Patients in the period from 1977 to 1992. The first episode of acute pancreatitis was identified in the cohort. The observed number...... of patients with acute pancreatitis was compared with expected numbers on the basis of age, sex, and calendar-specific incidence rates in the general population. RESULTS: Overall, 15,526 patients were discharged and followed up for 112,824 person-years. The standardized incidence ratio (SIR) for acute...

  3. Septic arthritis and acute rheumatic fever in children: the diagnostic value of serological inflammatory markers.

    Science.gov (United States)

    Mistry, Raakhi M; Lennon, Diana; Boyle, Matthew J; Chivers, Karel; Frampton, Chris; Nicholson, Ross; Crawford, Haemish

    2015-01-01

    Joint pain and raised inflammatory markers are features of both acute rheumatic fever (ARF) and septic arthritis, often posing a diagnostic challenge to clinicians. Important differences in the presenting serological inflammatory marker profile may assist patient diagnosis, however, as clinical experience suggests that ARF is associated with a higher erythrocyte sedimentation rate (ESR), whereas other serological markers may be similarly elevated in these 2 conditions. The goal of this study was to determine the diagnostic value of serological inflammatory markers and white cell count (WCC) in children presenting with acute joint pain secondary to ARF or septic arthritis. Data were obtained from the Auckland regional rheumatic fever database and hospital computer records between 2005 and 2012. Records of all patients under the age of 16 years who were admitted with a new diagnosis of ARF or septic arthritis were analyzed. The diagnosis of ARF was defined on the basis of the New Zealand modification of the Jones Criteria, and the diagnosis of septic arthritis was defined on the basis of joint fluid cytology and culture. Baseline characteristics, serological inflammatory markers, and serum WCC were compared between the ARF and septic arthritis patient groups. Children with ARF displayed significantly higher ESR, higher serum C-reactive protein, and lower serum WCC than children with septic arthritis on presentation to hospital. In children presenting with monoarthritis, an ESR>64.5, serum WCCseptic arthritis. A significant proportion (30%) of children with the final diagnosis of ARF initially presented with monoarthritis; 14% of these children (5/34) had received nonsteroidal anti-inflammatory medication before hospital presentation, and 74% of these children (25/34) had abnormal echocardiograms on admission. ARF and septic arthritis are important diagnoses to consider in children presenting with acute joint pain in New Zealand. A significant proportion of patients

  4. Inflammatory response to titanium surfaces with fibrinogen and catalase coatings: an in vitro study.

    Science.gov (United States)

    Göransson, A; Gretzer, C; Tengvall, P; Wennerberg, A

    2007-03-01

    The aim of the present study was to evaluate the possibility to modulate the early inflammatory response in vitro by coating titanium surfaces with candidate proinflammatory (fibrinogen coated turned titanium "Fib") and antiinflammatory proteins (catalase on top of fibrinogen coated turned titanium "Cat"). Additionally, turned titanium surfaces (Ti) were used as controls. The discs were incubated with human mononuclear cells. Adhered cells were investigated with respect to number, viability, differentiation (acute marker 27E10 vs. chronic marker RM3/1), and cytokine production (TNF-alpha and IL-10), after 24 and 72 h. The results indicated that it is possible to modulate the inflammatory response with protein coatings. However, the strongest inflammatory response, indicated by increased number of adhered cells and release of pro and antiinflammatory mediators, was induced by Cat. Furthermore, the cytokine production on this surface was not sensitive to LPS stimulation. Differentiation measured as the expression of the chronic cell surface marker, dominated after 72 h for all surface modifications and Cat displayed an increased number compared to the others. A decrease in the total number of adhered cells and amounts of TNF-alpha were observed on all surfaces over time. The cell viability was, in general, high for all tested surfaces. In conclusion, the study proved it possible to influence the early inflammatory response in vitro by immobilizing protein coatings to titanium surfaces. However, the catalase surface demonstrated the strongest inflammatory response, and the possibility to selectively use the potent antiinflammatory capacity of catalase needs to be further evaluated.

  5. Modulation of Hemostatic and Inflammatory Responses by Leptospira Spp.

    Directory of Open Access Journals (Sweden)

    Mônica L Vieira

    2016-05-01

    Full Text Available Leptospirosis is a worldwide spread zoonotic and neglected infectious disease of human and veterinary concern that is caused by pathogenic Leptospira species. In severe infections, hemostatic impairments such as coagulation/fibrinolysis dysfunction are frequently observed. These complications often occur when the host response is controlled and/or modulated by the bacterial pathogen. In the present investigation, we aimed to analyze the modulation of the hemostatic and inflammatory host responses by the bacterial pathogen Leptospira. The effects of leptospires and their secreted products on stimulation of human intrinsic and extrinsic pathways of coagulation were investigated by means of altered clotting times, assembly and activation of contact system and induction of tissue factor. We show that both extrinsic and intrinsic coagulation cascades are modulated in response to Leptospira or leptospiral secreted proteins. We further find that the pro-inflammatory mediator bradykinin is released following contact activation at the bacterial surface and that pro-coagulant microvesicles are shed from monocytes in response to infection. Also, we show that human leptospirosis patients present higher levels of circulating pro-coagulant microvesicles than healthy individuals. Here we show that both pathways of the coagulation system are modulated by leptospires, possibly leading to altered hemostatic and inflammatory responses during the disease. Our results contribute to the understanding of the leptospirosis pathophysiological mechanisms and may open new routes for the discovery of novel treatments for the severe manifestations of the disease.

  6. Modulation of Hemostatic and Inflammatory Responses by Leptospira Spp.

    Science.gov (United States)

    Vieira, Mônica L; Naudin, Clément; Mörgelin, Matthias; Romero, Eliete C; Nascimento, Ana Lucia T O; Herwald, Heiko

    2016-05-01

    Leptospirosis is a worldwide spread zoonotic and neglected infectious disease of human and veterinary concern that is caused by pathogenic Leptospira species. In severe infections, hemostatic impairments such as coagulation/fibrinolysis dysfunction are frequently observed. These complications often occur when the host response is controlled and/or modulated by the bacterial pathogen. In the present investigation, we aimed to analyze the modulation of the hemostatic and inflammatory host responses by the bacterial pathogen Leptospira. The effects of leptospires and their secreted products on stimulation of human intrinsic and extrinsic pathways of coagulation were investigated by means of altered clotting times, assembly and activation of contact system and induction of tissue factor. We show that both extrinsic and intrinsic coagulation cascades are modulated in response to Leptospira or leptospiral secreted proteins. We further find that the pro-inflammatory mediator bradykinin is released following contact activation at the bacterial surface and that pro-coagulant microvesicles are shed from monocytes in response to infection. Also, we show that human leptospirosis patients present higher levels of circulating pro-coagulant microvesicles than healthy individuals. Here we show that both pathways of the coagulation system are modulated by leptospires, possibly leading to altered hemostatic and inflammatory responses during the disease. Our results contribute to the understanding of the leptospirosis pathophysiological mechanisms and may open new routes for the discovery of novel treatments for the severe manifestations of the disease.

  7. LPS-induced lung inflammation in marmoset monkeys - an acute model for anti-inflammatory drug testing.

    Directory of Open Access Journals (Sweden)

    Sophie Seehase

    Full Text Available Increasing incidence and substantial morbidity and mortality of respiratory diseases requires the development of new human-specific anti-inflammatory and disease-modifying therapeutics. Therefore, new predictive animal models that closely reflect human lung pathology are needed. In the current study, a tiered acute lipopolysaccharide (LPS-induced inflammation model was established in marmoset monkeys (Callithrix jacchus to reflect crucial features of inflammatory lung diseases. Firstly, in an ex vivo approach marmoset and, for the purposes of comparison, human precision-cut lung slices (PCLS were stimulated with LPS in the presence or absence of the phosphodiesterase-4 (PDE4 inhibitor roflumilast. Pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α and macrophage inflammatory protein-1 beta (MIP-1β were measured. The corticosteroid dexamethasone was used as treatment control. Secondly, in an in vivo approach marmosets were pre-treated with roflumilast or dexamethasone and unilaterally challenged with LPS. Ipsilateral bronchoalveolar lavage (BAL was conducted 18 hours after LPS challenge. BAL fluid was processed and analyzed for neutrophils, TNF-α, and MIP-1β. TNF-α release in marmoset PCLS correlated significantly with human PCLS. Roflumilast treatment significantly reduced TNF-α secretion ex vivo in both species, with comparable half maximal inhibitory concentration (IC(50. LPS instillation into marmoset lungs caused a profound inflammation as shown by neutrophilic influx and increased TNF-α and MIP-1β levels in BAL fluid. This inflammatory response was significantly suppressed by roflumilast and dexamethasone. The close similarity of marmoset and human lungs regarding LPS-induced inflammation and the significant anti-inflammatory effect of approved pharmaceuticals assess the suitability of marmoset monkeys to serve as a promising model for studying anti-inflammatory drugs.

  8. The ultrasonographic findings of acute pelvic inflammatory disease

    International Nuclear Information System (INIS)

    Choi, Yeon Nam; Park, Jai Soung; Lee, Hae Kyung; Chung, Moo Chan; Lee, Beong Ho; Kim, Ki Jung

    1987-01-01

    Although ultrasonographic findings of female pelvic mass are frequently reported, those of acute PID are not well established. But differentiation of fluid collection and mass lesion of PID is exactly made by ultrasonography. We analysed the ultrasonographic findings in 26 cases of acute PID having satisfactory operative or histological proofs, examined at Soonchunhyang University Hospital from Oct. 1985 to Feb. 1987. The results were as follows: 1. The age was ranged from 17 years to 53 years of age and the majority was between 21 years and 50 years of age. 2. Ultrasonographic findings are classified to fluid collection in cul de sac 17, tuboovarian abscess, 7 pyosalpix 2, endometritis 1 and normal 2 cases. 3. In cases of pelvic mass formation, their ecnogenecity were cystic form in 6 cases (22%), mixed form in 19 cases (71%), solid form in 2 cases (7%), and shapes were mainly ovoid with irregular, ill-defined margin. The location of mass is unilateral in 17 cases (63%) bilateral in 10 cases (37%)

  9. Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

    Directory of Open Access Journals (Sweden)

    Preisinger Rudolf

    2010-01-01

    Full Text Available Abstract Background Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. Methods Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR. These investigations were accomplished by MHC genotyping and a PCR screen for Marek's disease virus (MDV. Results Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelin-bound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. Conclusions The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift.

  10. Effect of silica particle size on macrophage inflammatory responses.

    Directory of Open Access Journals (Sweden)

    Toshimasa Kusaka

    Full Text Available Amorphous silica particles, such as nanoparticles (<100 nm diameter particles, are used in a wide variety of products, including pharmaceuticals, paints, cosmetics, and food. Nevertheless, the immunotoxicity of these particles and the relationship between silica particle size and pro-inflammatory activity are not fully understood. In this study, we addressed the relationship between the size of amorphous silica (particle dose, diameter, number, and surface area and the inflammatory activity (macrophage phagocytosis, inflammasome activation, IL-1β secretion, cell death and lung inflammation. Irrespective of diameter size, silica particles were efficiently internalized by mouse bone marrow-derived macrophages via an actin cytoskeleton-dependent pathway, and induced caspase-1, but not caspase-11, activation. Of note, 30 nm-1000 nm diameter silica particles induced lysosomal destabilization, cell death, and IL-1β secretion at markedly higher levels than did 3000 nm-10000 nm silica particles. Consistent with in vitro results, intra-tracheal administration of 30 nm silica particles into mice caused more severe lung inflammation than that of 3000 nm silica particles, as assessed by measurement of pro-inflammatory cytokines and neutrophil infiltration in bronchoalveolar lavage fluid of mice, and by the micro-computed tomography analysis. Taken together, these results suggest that silica particle size impacts immune responses, with submicron amorphous silica particles inducing higher inflammatory responses than silica particles over 1000 nm in size, which is ascribed not only to their ability to induce caspase-1 activation but also to their cytotoxicity.

  11. Inflammatory, lipid, and body composition responses to interval training or moderate aerobic training.

    Science.gov (United States)

    Elmer, David J; Laird, Richard H; Barberio, Matthew D; Pascoe, David D

    2016-03-01

    The goal of this study was to compare the effect of work- and duration-matched interval training (HIIT) versus moderate aerobic endurance training (ET) on acute and chronic inflammation, along with changes in the lipid profile, to determine which may be more beneficial for improving cardiovascular health. Twelve sedentary males (maximal oxygen consumption = 41.6 ± 5.4 mL kg(-1) min(-1)) completed 8 weeks of aerobic interval training or moderate aerobic training, with variables including C-reactive protein (CRP) for chronic inflammation, interleukin-6 (IL-6) response for the acute inflammatory response, plasma concentrations of high-density lipoprotein (HDL), total cholesterol (TC), triglycerides (TRG), and low-density lipoprotein, and body composition measured before and after the training period. HIIT decreased plasma TRG from 92 ± 32 to 61 ± 12 mg dL(-1), which was significantly different from ET, while ET improved the TC:HDL ratio from 4.67 ± 0.85 to 4.07 ± 0.96 and reduced the percentage of android fat from 36.78 ± 9.60 to 34.18 ± 11.39 %. Neither training protocol resulted in an acute IL-6 response on the first nor the last day of exercise, a change in chronic levels of CRP, or a significant increase in HDL, despite previous research finding these changes. It seems that in order to maximize the health outcomes from physical activity, both HIIT and ET should be included. The acute inflammatory response and reductions in chronic inflammation resulting from exercise training may not be as common as the literature suggests.

  12. Dark chocolate attenuates intracellular pro-inflammatory reactivity to acute psychosocial stress in men: A randomized controlled trial.

    Science.gov (United States)

    Kuebler, Ulrike; Arpagaus, Angela; Meister, Rebecca E; von Känel, Roland; Huber, Susanne; Ehlert, Ulrike; Wirtz, Petra H

    2016-10-01

    Flavanol-rich dark chocolate consumption relates to lower risk of cardiovascular mortality, but underlying mechanisms are elusive. We investigated the effect of acute dark chocolate consumption on inflammatory measures before and after stress. Healthy men, aged 20-50years, were randomly assigned to a single intake of either 50g of flavanol-rich dark chocolate (n=31) or 50g of optically identical flavanol-free placebo-chocolate (n=34). Two hours after chocolate intake, both groups underwent the 15-min Trier Social Stress Test. We measured DNA-binding-activity of the pro-inflammatory transcription factor NF-κB (NF-κB-BA) in peripheral blood mononuclear cells, as well as plasma and whole blood mRNA levels of the pro-inflammatory cytokines IL-1β and IL-6, and the anti-inflammatory cytokine IL-10, prior to chocolate intake as well as before and several times after stress. We also repeatedly measured the flavanol epicatechin and the stress hormones epinephrine and cortisol in plasma and saliva, respectively. Compared to the placebo-chocolate-group, the dark-chocolate-group revealed a marginal increase in IL-10 mRNA prior to stress (p=0.065), and a significantly blunted stress reactivity of NF-κB-BA, IL-1β mRNA, and IL-6 mRNA (p's⩽0.036) with higher epicatechin levels relating to lower pro-inflammatory stress reactivity (p's⩽0.033). Stress hormone changes to stress were controlled. None of the other measures showed a significant chocolate effect (p's⩾0.19). Our findings indicate that acute flavanol-rich dark chocolate exerts anti-inflammatory effects both by increasing mRNA expression of the anti-inflammatory cytokine IL-10 and by attenuating the intracellular pro-inflammatory stress response. This mechanism may add to beneficial effects of dark chocolate on cardiovascular health. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Vaccination elicits a prominent acute phase response in horses.

    Science.gov (United States)

    Andersen, Susanne A; Petersen, Henrik H; Ersbøll, Annette K; Falk-Rønne, Jørgen; Jacobsen, Stine

    2012-02-01

    European and American guidelines for vaccination against tetanus and influenza in horses recommend annual and annual/semi-annual vaccinations, respectively, against the two pathogens. Too-frequent vaccination may, however, have adverse effects, among other things because an inflammatory response is elicited with subsequent alterations in homeostasis. The objective of the study was to compare the acute phase response (APR) in 10 horses following administration of two different types of vaccines, namely, an inactivated Immune Stimulating COMplex (ISCOM) vaccine and a live recombinant vector vaccine. Blood was sampled before and after vaccination to measure levels of serum amyloid A (SAA), fibrinogen, white blood cell counts (WBC) and iron. Vaccination induced a prominent APR with increased WBC, elevated blood levels of SAA and fibrinogen, and decreased serum iron concentrations. The ISCOM vaccine caused significantly (Phorse owners about convalescence after vaccination. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. L-alanyl-glutamine pretreatment attenuates acute inflammatory response in children submitted to palatoplasty Pré-tratamento com L-alanil-glutamina atenua a resposta inflamatória aguda em crianças submetidas à palatoplastia

    Directory of Open Access Journals (Sweden)

    José Ferreira da Cunha Filho

    2011-01-01

    Full Text Available PURPOSE: To evaluate the effects of L-alanyl-glutamine (L-Ala-Gln pretreatment on oxidative stress, glycemic control and inflammatory response in children submitted to palatoplasty. METHODS: Thirty male children scheduled for routine palatoplasty, age range 2-10 years, were randomly assigned to 2 groups (n=15: Group A (saline, control and Group B (L-Ala-Gln. Group A received normal saline 100 ml, delivered intravenously by infusion pump over 3 hours preceding surgical procedure. Group B was treated with L-Ala-Gln, 20% solution (0.5g/Kg, adding saline to complete 100ml. Peripheral venous blood samples were collected at 5 different time-points: T1- at the beginning of the study, 3 h prior to the surgical procedure; T2- at the end of the infusion (before the surgical procedure, T3- at the end of the surgical procedure, T4- 6 h postoperative and T5- 12 h postoperative. Parameters analyzed included glutathione (GSH, thiobarbituric acid reactive substances (TBARS, glucose, insulin, C-reactive protein (CRP and interleukin-6 (IL-6. RESULTS: No statistically significant differences were found between groups comparing glucose, insulin, TBARS, GSH and IL-6 levels. However, glucose levels increased (P OBJETIVO: Avaliar os efeitos do pré-tratamento com L-alanil-glutamina (L-Ala-Gln sobre o estresse oxidativo, o controle glicêmico e a resposta inflamatória em crianças submetidas à palatoplastia. MÉTODOS: Trinta crianças do sexo masculino, agendadas para palatoplastia, faixa etária 2-10 anos, foram distribuídas aleatoriamente em dois grupos (n = 15: Grupo A (salina, controle e Grupo B (L-Ala-Gln. O grupo A recebeu solução salina 0,9% 100 ml, administrado por via intravenosa utilizando uma bomba de infusão durante 3 horas anteriores ao procedimento cirúrgico. O grupo B foi tratado com L-Ala-Gln, solução a 20% (0,5 g/kg, acrescentando soro fisiológico até completar 100 ml. Amostras de sangue venoso periférico foram coletadas em cinco momentos

  15. Systemic inflammatory response syndrome: a case of septic shock

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    Nicolò Gentiloni Silveri

    2008-09-01

    Full Text Available An elderly, diabetic male, with severe sepsis, swiftly treated with antibiotics that were efficacious in vitro against the E. Coli isolated in his blood, rapidly slides into multiple organ dysfunction syndrome and dies of septic shock after a month in intensive care, despite receiving appropriate pain relief and aetiopathogenetic therapy. This event provides us with the opportunity to take a new look at systemic inflammatory response syndrome and a critical review of the relative therapy

  16. Engineering macrophages to control the inflammatory response and angiogenesis.

    Science.gov (United States)

    Eaton, K V; Yang, H L; Giachelli, C M; Scatena, M

    2015-12-10

    Macrophage (MΦ) dysregulation is increasingly becoming recognized as a risk factor for a number of inflammatory complications including atherosclerosis, cancer, and the host response elicited by biomedical devices. It is still unclear what roles the pro-inflammatory (M1) MΦ and pro-healing (M2) MΦ phenotypes play during the healing process. However, it has been shown that a local overabundance of M1 MΦs can potentially lead to a chronically inflamed state of the tissue; while a local over-exuberant M2 MΦ response can lead to tissue fibrosis and even promote tumorigenesis. These notions strengthen the argument that the tight temporal regulation of this phenotype balance is necessary to promote inflammatory resolution that leads to tissue homeostasis. In this study, we have engineered pro-inflammatory MΦs, MΦ-cTLR4 cells, which can be activated to a M1-like MΦ phenotype with a small molecule, the chemical inducer of dimerization (CID) drug. The MΦ-cTLR4 cells when activated with the CID drug, express increased levels of TNFα, IL-6, and iNOS. Activated MΦ-cTLR4 cells stay stimulated for at least 48h; once the CID drug is withdrawn, the MΦ-cTLR4 cells return to baseline state within 18h. Further, in vitro CID-activated MΦ-cTLR4 cells induce upregulation of VCAM-1 and ICAM-1 on endothelial cells (EC) in a TNFα-dependent manner. With the ability to specifically modulate the MФ-cTLR4 cells with the presence or absence of a small molecule, we now have the tool necessary to observe a primarily M1 MФ response during inflammation. By isolating this phase of the wound healing response, it may be possible to determine conditions for ideal healing. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Elevated white cell count in acute coronary syndromes: relationship to variants in inflammatory and thrombotic genes

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    Cannon Christopher P

    2004-06-01

    Full Text Available Abstract Background Elevated white blood cell counts (WBC in acute coronary syndromes (ACS increase the risk of recurrent events, but it is not known if this is exacerbated by pro-inflammatory factors. We sought to identify whether pro-inflammatory genetic variants contributed to alterations in WBC and C-reactive protein (CRP in an ACS population. Methods WBC and genotype of interleukin 6 (IL-6 G-174C and of interleukin-1 receptor antagonist (IL1RN intronic repeat polymorphism were investigated in 732 Caucasian patients with ACS in the OPUS-TIMI-16 trial. Samples for measurement of WBC and inflammatory factors were taken at baseline, i.e. Within 72 hours of an acute myocardial infarction or an unstable angina event. Results An increased white blood cell count (WBC was associated with an increased C-reactive protein (r = 0.23, p 3 (95% CI = -0.41, 0.77, and -0.03/mm3 (95% CI = -0.55, 0.86 for IL1RN. Moreover, the composite endpoint was not significantly affected by an interaction between WBC and the IL1 (p = 0.61 or IL6 (p = 0.48 genotype. Conclusions Cytokine pro-inflammatory genetic variants do not influence the increased inflammatory profile of ACS patients.

  18. Synthesis, acute toxicity and anti-inflammatory effect of bornyl salicylate, a salicylic acid derivative.

    Science.gov (United States)

    Vasconcelos, Renata Marcia Costa; Leite, Fagner Carvalho; Leite, Jacqueline Alves; Rodrigues Mascarenhas, Sandra; Rodrigues, Luis Cezar; Piuvezam, Marcia Regina

    2012-12-01

    Bornyl salicylate (BS) is a salicylic derivative, obtained by sterification of salicylic acid and monoterpene (-)-borneol, and its topical use in inflammatory diseases was described in the early 20th century. It is also known that borneol presents neuroprotective, genoprotective and analgesic properties. The purpose of this study was to evaluate BS in experimental models of acute inflammation. The toxicity of BS was analyzed by measuring water and food intake, weight, mortality and weight of main organs. To assess its anti-inflammatory effect, BS-treated mice were challenged with carrageenan, prostaglandin E2 (PGE2), bradikynin (BK) or histamine (HIS)-induced paw edema, zymosan-induced peritonitis and vascular permeability induced by acetic acid. Nitric oxide (NO) production was analyzed in peritoneal macrophage cultures. There was no sign of acute toxicity of BS in male and female mice. Furthermore, treatment with BS was significantly (p acetic acid were also reduced in BS-treated animals. In vitro, BS (10 µg/mL) reduced NO production in LPS-stimulated macrophages. These data suggest that BS has an anti-inflammatory effect, which is related, at least in part, with decrease of mediators as PGE2, NO and pro-inflammatory cytokines. However, further studies should be done to explore its potential as an anti-inflammatory drug.

  19. Evaluation of Mediators Associated with the Inflammatory Response in Prostate Cancer Patients Undergoing Radiotherapy

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    Nice Bedini

    2018-01-01

    Full Text Available A recent “hot topic” in prostate cancer radiotherapy is the observed association between acute/late rectal toxicity and the presence of abdominal surgery before radiotherapy. The exact mechanism is unclear. Our working hypothesis was that a previous surgery may influence plasma level of inflammatory molecules and this might result in enhanced radiosensitivity. We here present results on the feasibility of monitoring the expression of inflammatory molecules during radiotherapy. Plasma levels of a panel of soluble mediators associated with the inflammatory response were measured in prostate cancer patients undergoing radical radiotherapy. We measured 3 cytokines (IL-1b, IL-6, and TNF alpha, 2 chemokines (CCL2 and CXCL8, and the long pentraxin PTX3. 20 patients were enrolled in this feasibility evaluation. All patients were treated with IMRT at 78 Gy. 3/20 patients reported grade 2 acute rectal toxicity, while 4/20 were scored as grade 2 late toxicity. CCL2 was the most interesting marker showing significant increase during and after radiotherapy. CCL2 levels at radiotherapy end could be modelled using linear regression including basal CCL2, age, surgery, hypertension, and use of anticoagulants. The 4 patients with late toxicity had CCL2 values at radiotherapy end above the median value. This trial is registered with ISRCTN64979094.

  20. Immunomodulation of the allergic inflammatory response: new developments.

    Science.gov (United States)

    Araujo, Maria I; Campos, Regis A; Cardoso, Luciana S; Oliveira, Sergio C; Carvalho, Edgar M

    2010-06-01

    Studies of the molecular mechanisms associated with allergic diseases have lead to a better understanding of the complex processes that underlie their pathogenesis. These mechanisms involve Th2- and Th1-type cells and also some recently described cytokines, such as IL-25 and IL-33. Regulatory mechanisms of allergic inflammation have also been identified. For instance, IL-10, a cytokine produced by many cell types, promotes a decrease in IgE production, and inhibits the release of histamine and other inflammatory mediators by mast cells. Recently, a variety of regulatory cells have been discovered, which, either by direct contact or through the production of IL-10 and/or TGF-beta, can inhibit the allergic inflammatory response. IL-10 is produced in high levels by cells of helminth-infected individuals. There is some evidence that such infections protect against the development of allergic diseases. In asthmatic individuals living in endemic areas of schistosomiasis, it has been shown in in vitro studies that there is a modulation of the Th2 response, both by mechanisms involving IL-10, which is produced mainly by monocytes and CD4+CD25+ T regulatory cells, and also by the expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) in CD4+ T cells. Studies using parasite antigens to induce the modulation of allergic inflammatory response are being conducted by several groups of researchers and represent new perspectives for the treatment of allergic diseases.

  1. INFLAMMATORY MARKERS IN ACUTE ISCHAEMIC STROKE IN RELATION TO CLINICAL SEVERITY AND EARLY OUTCOME

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    S. Gopi

    2018-01-01

    Full Text Available BACKGROUND Biochemical markers of inflammation could be useful to predict severity of stroke in acute phase. Stroke is the third cause of mortality and the first cause of disability. Recent literature have demonstrated that inflammation contributes to all phases of atherosclerosis. The results of researchers suggest that atherosclerosis is an inflammatory disease. The aim of the study is to assess the1. Level of peripheral inflammatory markers in acute ischaemic stroke and their relation to severity of acute stroke. 2. Value of inflammatory markers in predicting the short-term outcome and disability at the end of six months. MATERIALS AND METHODS This is a prospective case control study for 6 months done from September 2014 to August 2016 in 100 patients of acute ischaemic stroke within first 5 days of symptom onset in comparison >18 years of age with 50 age and sex matched controls. Blood samples for all cases and controls were sent for erythrocyte sedimentation rate, Neutrophil-to-Lymphocyte Ratio (NLR, hs-C-reactive protein, mean platelet volume, serum ferritin, serum albumin and S. gamma-glutamyl transferase at admission. RESULTS The mean values of ESR, NLR, hs-CRP in all the cases are higher when compared to the controls and are statistically significant, whereas the mean values of MPV, S. ferritin, S. albumin and GGT in cases are lower when compared to controls, but are within normal range and difference is statistically significant except ferritin. ESR, hs-CRP has significant correlation with severity of acute ischaemic stroke. The mean values of these markers increased with increase in severity. Serum albumin has significant correlation with severity of acute ischaemic stroke with mean values of these markers decreasing with increase in severity of stroke. There is no significant correlation of the inflammatory markers in present study with the short-term outcome. CONCLUSION Inflammation plays an important role in the pathogenesis of non

  2. Acute Pelvic Inflammatory Disease in Cameroon: A Cross Sectional ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    found that they can be responsible for urethritis in men, cervicitis and PID in women10,11. In our settings, many women with pelvic infection have their complaints resolved when genital tract mycoplasmas are identified and treated. This shows that screening for genital tract mycoplasmas should be as frequent as screening ...

  3. Microglial depletion alters the brain neuroimmune response to acute binge ethanol withdrawal.

    Science.gov (United States)

    Walter, T Jordan; Crews, Fulton T

    2017-04-20

    Recent studies have implicated microglia-the resident immune cells of the brain-in the pathophysiology of alcoholism. Indeed, post-mortem alcoholic brains show increased microglial markers and increased immune gene expression; however, the effects of ethanol on microglial functioning and how this impacts the brain remain unclear. In this present study, we investigate the effects of acute binge ethanol on microglia and how microglial depletion changes the brain neuroimmune response to acute binge ethanol withdrawal. C57BL/6J mice were treated intragastrically with acute binge ethanol for time course and dose-response studies. Cultured mouse BV2 microglia-like cells were treated with ethanol in vitro for time course studies. Mice were also administered the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia from the brain. These mice were subsequently treated with acute binge ethanol and sacrificed during withdrawal. Brain and BV2 mRNA were isolated and assessed using RT-PCR to examine expression of microglial and neuroimmune genes. Acute binge ethanol biphasically changed microglial (e.g., Iba1, CD68) gene expression, with initial decreases during intoxication and subsequent increases during withdrawal. Acute ethanol withdrawal dose dependently increased neuroimmune gene (e.g., TNFα, Ccl2, IL-1ra, IL-4) expression beginning at high doses. BV2 cells showed biphasic changes in pro-inflammatory (e.g., TNFα, Ccl2) gene expression following ethanol treatment in vitro. Administration of PLX5622 depleted microglia from the brains of mice. Although some neuroimmune genes were reduced by microglial depletion, many others were unchanged. Microglial depletion blunted pro-inflammatory (e.g., TNFα, Ccl2) gene expression and enhanced anti-inflammatory (e.g., IL-1ra, IL-4) gene expression during acute binge ethanol withdrawal. These studies find acute binge ethanol withdrawal increases microglial and neuroimmune gene expression. Ethanol exposure

  4. Obese mice exhibit an altered behavioural and inflammatory response to lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Catherine B. Lawrence

    2012-09-01

    Obesity is associated with an increase in the prevalence and severity of infections. Genetic animal models of obesity (ob/ob and db/db mice display altered centrally-mediated sickness behaviour in response to acute inflammatory stimuli such as lipopolysaccharide (LPS. However, the effect of diet-induced obesity (DIO on the anorectic and febrile response to LPS in mice is unknown. This study therefore determined how DIO and ob/ob mice respond to a systemic inflammatory challenge. C57BL/6 DIO and ob/ob mice, and their respective controls, were given an intraperitoneal (i.p. injection of LPS. Compared with controls, DIO and ob/ob mice exhibited an altered febrile response to LPS (100 μg/kg over 8 hours. LPS caused a greater and more prolonged anorexic effect in DIO compared with control mice and, in ob/ob mice, LPS induced a reduction in food intake and body weight earlier than it did in controls. These effects of LPS in obese mice were also seen after a fixed dose of LPS (5 μg. LPS (100 μg/kg induced Fos protein expression in several brain nuclei of control mice, with fewer Fos-positive cells observed in the brains of obese mice. An altered inflammatory response to LPS was also observed in obese mice compared with controls: changes in cytokine expression and release were detected in the plasma, spleen, liver and peritoneal macrophages in obese mice. In summary, DIO and ob/ob mice displayed an altered behavioural response and cytokine release to systemic inflammatory challenge. These findings could help explain why obese humans show increased sensitivity to infections.

  5. Heterogeneity of systemic inflammatory responses to periodontal therapy.

    Science.gov (United States)

    Behle, Jan H; Sedaghatfar, Michael H; Demmer, Ryan T; Wolf, Dana L; Celenti, Romanita; Kebschull, Moritz; Belusko, Paul B; Herrera-Abreu, Miriam; Lalla, Evanthia; Papapanou, Panos N

    2009-04-01

    We investigated the effect of comprehensive periodontal therapy on the levels of multiple systemic inflammatory biomarkers. Thirty patients with severe periodontitis received comprehensive periodontal therapy within a 6-week period. Blood samples were obtained at: 1-week pre-therapy (T1), therapy initiation (T2), treatment completion (T3), and 4 weeks thereafter (T4). We assessed the plasma concentrations of 19 biomarkers using multiplex assays, and serum IgG antibodies to periodontal bacteria using checkerboard immunoblotting. At T2 and T4, dental plaque samples were analysed using checkerboard hybridizations. At T3, PAI-1, sE-selectin, sVCAM-1, MMP-9, myeloperoxidase, and a composite summary inflammatory score (SIS) were significantly reduced. However, only sE-selectin, sICAM, and serum amyloid P sustained a reduction at T4. Responses were highly variable: analyses of SIS slopes between baseline and T4 showed that approximately 1/3 and 1/4 of the patients experienced a marked reduction and a pronounced increase in systemic inflammation, respectively, while the remainder were seemingly unchanged. Changes in inflammatory markers correlated poorly with clinical, microbiological and serological markers of periodontitis. Periodontal therapy resulted in an overall reduction of systemic inflammation, but the responses were inconsistent across subjects and largely not sustainable. The determinants of this substantial heterogeneity need to be explored further.

  6. Haemophilus influenzae induces steroid-resistant inflammatory responses in COPD.

    Science.gov (United States)

    Cosío, Borja G; Jahn, Andreas; Iglesias, Amanda; Shafiek, Hanaa; Busquets, Xavier; Agustí, Alvar

    2015-12-07

    Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder partially resistant to glucocorticoids. A reduced histone deacetylase (HDAC) activity has been proposed to explain this resistance. Haemophilus influenzae frequently colonizes the airways of COPD patients, where it enhances inflammation. The effects of Haemophilus influenzae on HDAC activity have not been investigated before. The effects of the presence or absence of Haemophilus influenzae ex-vivo and in vitro were studied. To this end, we determined: (1) cytokine release in alveolar macrophages (AM) from 7 patients with COPD, 5 healthy smokers, 6 healthy non-smokers and (2) HDAC activity, nuclear factor kappa B (NF-κB) activation in a macrophage-like cell line (PMA-transformed U937 cells) co-cultured with epithelial cells. Experiments were repeated with dexamethasone (1 μM) and/or the HDAC enhancer theophylline (10 μM). Haemophilus influenzae induced a steroid-resistant inflammatory response in AM from COPD and controls and decreased HDAC activity, activated NF-κB and induced the secretion of several cytokines (IL-6, IL-8, IL-1β, IL-10 and TNF-α) (p Haemophilus influenzae reduces HDAC activity and induces a NF-κB mediated inflammatory response that is only partially suppressed by glucocorticoids irrespective of having COPD. Yet, the latter can be fully restored by targeting HDAC activity.

  7. Non-canonical Glucocorticoid Receptor Transactivation of gilz by Alcohol Suppresses Cell Inflammatory Response

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    Hang Pong Ng

    2017-06-01

    Full Text Available Acute alcohol exposure suppresses cell inflammatory response. The underlying mechanism has not been fully defined. Here we report that alcohol was able to activate glucocorticoid receptor (GR signaling in the absence of glucocorticoids (GCs and upregulated glucocorticoid-induced leucine zipper (gilz, a prominent GC-responsive gene. Such a non-canonical activation of GR was not blocked by mifepristone, a potent GC competitor. The proximal promoter of gilz, encompassing five GC-responsive elements (GREs, was incorporated and tested in a luciferase reporter system. Deletion and/or mutation of the GREs abrogated the promoter responsiveness to alcohol. Thus, the GR–GRE interaction transduced the alcohol action on gilz. Alcohol induced GR nuclear translocation, which was enhanced by the alcohol dehydrogenase inhibitor fomepizole, suggesting that it was alcohol, not its metabolites, that engendered the effect. Gel mobility shift assay showed that unliganded GR was able to bind GREs and such interaction withstood clinically relevant levels of alcohol. GR knockout via CRISPR/Cas9 gene targeting or GILZ depletion via small RNA interference diminished alcohol suppression of cell inflammatory response to LPS. Thus, a previously unrecognized, non-canonical GR activation of gilz is involved in alcohol modulation of cell immune response.

  8. Systemic inflammatory response to smoking in chronic obstructive pulmonary disease: evidence of a gender effect.

    Directory of Open Access Journals (Sweden)

    Rosa Faner

    Full Text Available BACKGROUND: Tobacco smoking is the main risk factor of chronic obstructive pulmonary disease (COPD but not all smokers develop the disease. An abnormal pulmonary and systemic inflammatory response to smoking is thought to play a major pathogenic role in COPD, but this has never been tested directly. METHODS: We studied the systemic biomarker and leukocyte transcriptomic response (Affymetrix microarrays to smoking exposure in 10 smokers with COPD and 10 smokers with normal spirometry. We also studied 10 healthy never smokers (not exposed to smoking as controls. Because some aspects of COPD may differ in males and females, and the inflammatory response to other stressors (infection might be different in man and women, we stratified participant recruitment by sex. Differentially expressed genes were validated by q-PCR. Ontology enrichment was evaluated and interaction networks inferred. RESULTS: Principal component analysis identified sex differences in the leukocyte transcriptomic response to acute smoking. In both genders, we identified genes that were differentially expressed in response to smoking exclusively in COPD patients (COPD related signature or smokers with normal spirometry (Smoking related signature, their ontologies and interaction networks. CONCLUSIONS: The use of an experimental intervention (smoking exposure to investigate the transcriptomic response of peripheral leukocytes in COPD is a step beyond the standard case-control transcriptomic profiling carried out so far, and has facilitated the identification of novel COPD and Smoking expression related signatures which differ in males and females.

  9. Regulatory T Cells Protect Fine Particulate Matter-Induced Inflammatory Responses in Human Umbilical Vein Endothelial Cells

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    Wen-cai Zhang

    2014-01-01

    Full Text Available Objective. To investigate the role of CD4+CD25+ T cells (Tregs in protecting fine particulate matter (PM- induced inflammatory responses, and its potential mechanisms. Methods. Human umbilical vein endothelial cells (HUVECs were treated with graded concentrations (2, 5, 10, 20, and 40 µg/cm2 of suspension of fine particles for 24h. For coculture experiment, HUVECs were incubated alone, with CD4+CD25− T cells (Teff, or with Tregs in the presence of anti-CD3 monoclonal antibodies for 48 hours, and then were stimulated with or without suspension of fine particles for 24 hours. The expression of adhesion molecules and inflammatory cytokines was examined. Results. Adhesion molecules, including vascular cell adhesion molecule-1 (VCAM-1 and intercellular adhesion molecule-1 (ICAM-1, and inflammatory cytokines, such as interleukin (IL- 6 and IL-8, were increased in a concentration-dependent manner. Moreover, the adhesion of human acute monocytic leukemia cells (THP-1 to endothelial cells was increased and NF-κB activity was upregulated in HUVECs after treatment with fine particles. However, after Tregs treatment, fine particles-induced inflammatory responses and NF-κB activation were significantly alleviated. Transwell experiments showed that Treg-mediated suppression of HUVECs inflammatory responses impaired by fine particles required cell contact and soluble factors. Conclusions. Tregs could attenuate fine particles-induced inflammatory responses and NF-κB activation in HUVECs.

  10. [Puncture scrotostomy--a treatment method in acute inflammatory diseases of the scrotal organs].

    Science.gov (United States)

    Shapoval, V I; Asimov, D A; Lesovoĭ, V N

    1989-01-01

    A method for the treatment of acute inflammatory diseases of the scrotal organs by means of puncture scrotostomy, which consists in passing the indwelling micro-irrigator into a cavity of the serous sheath of the testis and epididymis and administration via this route of antibacterial and resolving preparations for 4-5 days, is suggested. A method approved in treatment of 45 patients permits to avoid surgical intervention, and is highly effective.

  11. Chemical composition, acute toxicity, antioxidant and anti-inflammatory activities of Moroccan Tetraclinis articulata L.

    OpenAIRE

    El Jemli, Meryem; Kamal, Rabie; Marmouzi, Ilias; Doukkali, Zouhra; Bouidida, El Houcine; Touati, Driss; Nejjari, Rachid; El Guessabi, Lahcen; Cherrah, Yahia; Alaoui, Katim

    2016-01-01

    Hydro-distilled essential oil (EO) from the leaves of the western Mediterranean and Moroccan endemic plant Tetraclinis articulata was analyzed by GC/MS and examined for its acute toxicity on mice, in order to establish the safe doses. Furthermore, the anti-Inflammatory activity was evaluated based on carrageenan and trauma induced rats paw edema and the antioxidant potential has been investigated using different methods including DPPH radical-scavenging assay, Trolox equivalent antioxidant ca...

  12. Neuroendocrine Inflammatory Responses in Overweight/Obese Infants.

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    Ana Cristina Resende Camargos

    Full Text Available Childhood obesity is related to a cascade of neuroendocrine inflammatory changes. However, there remains a gap in the current literature regarding the possible occurrence of these changes in overweight/obese infants. The objective of this study was to evaluate adipokines, cortisol, brain-derived neurotrophic factor (BDNF and redox status in overweight/obese infants versus normal-weight peers. A cross-sectional study was conducted with 50 infants (25 in the overweight/obese group and 25 in the normal-weight group between 6 and 24 months. Plasma levels of leptin, adiponectin, resistin, soluble tumor necrosis factor (TNF receptors, chemokines, BDNF, serum cortisol and redox status were measured. Unpaired Student's t-test was used to analyze the results and a probability of p<0.05 was acceptable for rejection of the null hypothesis. The Pearson correlation was used to verify the association between the biomarkers analyzed in each group. Plasma levels of leptin (p = 0.0001, adiponectin (p = 0.0007 and BDNF (p = 0.003, and serum cortisol (p = 0.048 were significantly higher in overweight/obese infants than normal-weight infants. In contrast, the concentration of thiobarbituric acid reactive substances (TBARS (p = 0.004, and catalase (p = 0.045 and superoxide dismutase activity (p = 0.02 were lower in overweight/obese infants than normal-weight peers. All the results together indicate neuroendocrine inflammatory response changes in overweight/obese infants between 6 and 24 months. Although there is already an environment that predisposes for a subsequent pro-inflammatory response, neuroendocrine secretion changes that permit the control of the inflammatory process in this age interval can be observed.

  13. DMPD: Cytokine signaling modules in inflammatory responses. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18400190 Cytokine signaling modules in inflammatory responses. O'Shea JJ, Murray PJ.... Immunity. 2008 Apr;28(4):477-87. (.png) (.svg) (.html) (.csml) Show Cytokine signaling modules in inflamma...tory responses. PubmedID 18400190 Title Cytokine signaling modules in inflammatory responses. Authors O'Shea

  14. The changes and significance of serum inflammatory factors and hemodynamics in patients with acute cerebral infarction

    Directory of Open Access Journals (Sweden)

    Xiao-Wei Lu

    2016-01-01

    Full Text Available Objective: To investigate the changes of serum inflammatory factors and hemodynamics in patients with acute cerebral infarction and its clinical significance. Methods: A total of 55 cases of acute cerebral infarction (ACI patients as observation group, and cases of healthy physical examination were selected as the observation group, and 55 healthy persons as control group. ELISA method was used to detect inflammatory cytokines interleukin-6 (IL-6, interleukin-8 (IL-8, C-reactive protein (CRP and tumor necrosis factor (TNF-α level, WA- 880 heart and brain integrated digital hemodynamic monitor to detect bilateral carotid artery blood flow velocity, blood flow and peripheral resistance. Results: The serum levels of IL-8, CRP, IL-6 and TNF-α were higher in the observation group than in the control group, the difference was statistically significant (P<0.05. The blood flow velocity and blood flow velocity in the observation group were significantly lower than those in the control group. The difference was statistically significant (IL-8. With the increase of infarct size, serum IL-6, CRP, P<0.05 and TNF-α increased significantly (P<0.05. Conclusions: The changes of serum inflammatory factors and hemodynamic indexes can be used to judge the early cerebral infarction and the size of the infarct size of the index, the clinical dynamic monitoring of its changes in patients with acute cerebral infarction and the severity of the prognosis and the prognosis of the important significance of the judgment.

  15. Traumatic Reticuloperitonitis in Water Buffalo (Bubalus bubalis: Clinical Findings and the Associated Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Maged El-Ashker

    2013-01-01

    Full Text Available The present study was carried out to describe the clinical picture of traumatic reticuloperitonitis (TRP in water buffalo (Bubalus bubalis and to evaluate the inflammatory and immunologic responses for this clinical condition. Twenty-two buffalo with acute local TRP were monitored in our study. Additionally, 10 clinically healthy buffalo were randomly selected and served as controls. Acute local TRP was initially diagnosed by clinical examination and confirmed by ultrasonographic (USG examination and/or necropsy findings. Blood samples were collected from all examined buffalo to measure the respective levels of tumor necrosis factor alpha (TNF-α, interleukin (IL-1β, IL-6, IL-10 and interferon gamma (INF-γ, serum amyloid A (SAA, C-reactive protein (CRP, haptoglobin (Hp, fibrinogen (Fb, and serum sialic acid (SSA. It was found that TNF-α, IL-1β, IL-6, IL-10, SAA, CRP, Hp, Fb, and SSA were significantly higher in buffalo with TRP than the controls. Our findings suggest that the examined immunologic variables were helpful in documenting the inflammatory response in buffalo with TRP. However, their diagnostic usefulness only becomes apparent when considered in tandem with the clinical findings for any given animal, its anamnesis, and a subsequent USG assessment. Due to the frequent complications of TRP, more accurate indicators of its occurrence and severity would be useful.

  16. Preventively enteral application of immunoglobulin enriched colostrums milk can modulate postoperative inflammatory response

    Science.gov (United States)

    2013-01-01

    Several studies demonstrated acute inflammatory response following traumatic injury. Inflammatory response during surgical interventions was verified by a significant increase of endotoxin plasma levels and a decrease of the endotoxin neutralizing capacity (ENC). However, the incidence of elevated endotoxin levels was significantly higher (89%) than detected bacterial translocation (35%). Thus parts or products of Gram-negative bacteria seem to translocate more easily into the blood circulation than whole bacteria. Along with the bacterial translocation, the inflammatory response correlated directly with the severity of the surgical intervention. In comparison after major and minor surgery Interleukin-6 (IL-6) and C-reactive protein (CRP) was also significantly different. Similar effects in mediator release were shown during endovascular stent graft placement and open surgery in infrarenal aortic aneurysm. Open surgery demonstrated a significant stronger endotoxin translocation and a decrease of ENC. Strategies to prevent translocation seem to be sensible. Colostrum is the first milk produced by the mammary glands within the first days after birth. It contains a complex system of immune factors and has a long history of use in traditional medicine. Placebo-controlled studies verified that prophylactic oral application of immunoglobulin-enriched colostrum milk preparation diminishes perioperative endotoxemia, prevents reduction of ENC and reduces postoperative CRP-levels, suggesting a stabilization of the gut barrier. This effect may be caused by immunoglobulin transportation by the neonatal receptor FcRn of the mucosal epithelium. In conclusion, there is an association of perioperative endotoxemia and the subsequent increase in mediators of the acute phase reaction in surgical patients. A prophylactic oral application of colostrum milk is likely to stabilize the gut barrier i.e. reduces the influx of lipopolysaccharides arising from Gram-negative bacterial

  17. Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis

    International Nuclear Information System (INIS)

    Zhang, Wenyao; Li, Xuezhong; Xu, Tong; Ma, Mengru; Zhang, Yong; Gao, Ming-Qing

    2016-01-01

    Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. - Highlights: • Inflammatory BMEs affect the properties of BMFs during mastitis. • BMEs inhibited the proliferation and promoted the migration of BMFs. • BMEs enhanced secretion of inflammatory mediators and deposition of ECM in BMFs. • Changes of the properties of BMFs were mediated by specific signal molecules.

  18. Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenyao; Li, Xuezhong; Xu, Tong; Ma, Mengru [College of Veterinary Medicine, Northwest A& F University, Yangling 712100, Shaanxi (China); Zhang, Yong, E-mail: zhangyong1956@nwsuaf.edu.cn [College of Veterinary Medicine, Northwest A& F University, Yangling 712100, Shaanxi (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100, Shaanxi (China); Gao, Ming-Qing, E-mail: gaomingqing@nwsuaf.edu.cn [College of Veterinary Medicine, Northwest A& F University, Yangling 712100, Shaanxi (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100, Shaanxi (China)

    2016-11-15

    Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. - Highlights: • Inflammatory BMEs affect the properties of BMFs during mastitis. • BMEs inhibited the proliferation and promoted the migration of BMFs. • BMEs enhanced secretion of inflammatory mediators and deposition of ECM in BMFs. • Changes of the properties of BMFs were mediated by specific signal molecules.

  19. Non inflammatory boronate based glucose-responsive insulin delivery systems.

    Directory of Open Access Journals (Sweden)

    Indrani Dasgupta

    Full Text Available Boronic acids, known to bind diols, were screened to identify non-inflammatory cross-linkers for the preparation of glucose sensitive and insulin releasing agglomerates of liposomes (Agglomerated Vesicle Technology-AVT. This was done in order to select a suitable replacement for the previously used cross-linker, ConcanavalinA (ConA, a lectin known to have both toxic and inflammatory effects in vivo. Lead-compounds were selected from screens that involved testing for inflammatory potential, cytotoxicity and glucose-binding. These were then conjugated to insulin-encapsulating nanoparticles and agglomerated via sugar-boronate ester linkages to form AVTs. In vitro, the particles demonstrated triggered release of insulin upon exposure to physiologically relevant concentrations of glucose (10 mmoles/L-40 mmoles/L. The agglomerates were also shown to be responsive to multiple spikes in glucose levels over several hours, releasing insulin at a rate defined by the concentration of the glucose trigger.

  20. Effects of a Single Dose of Parecoxib on Inflammatory Response and Ischemic Tubular Injury Caused by Hemorrhagic Shock in Rats

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    Mariana Takaku

    2018-01-01

    Full Text Available Parecoxib, a selective COX-2 inhibitor, is used to improve analgesia in postoperative procedures. Here we evaluated whether pretreatment with a single dose of parecoxib affects the function, cell injury, and inflammatory response of the kidney of rats subjected to acute hemorrhage. Inflammatory response was determined according to serum and renal tissue cytokine levels (IL-1α, IL-1β, IL-6, IL-10, and TNF-α. Forty-four adult Wistar rats anesthetized with sevoflurane were randomized into four groups: placebo/no hemorrhage (Plc/NH; parecoxib/no hemorrhage (Pcx/NH; placebo/hemorrhage (Plc/H; and parecoxib/hemorrhage (Pcx/H. Pcx groups received a single dose of intravenous parecoxib while Plc groups received a single dose of placebo (isotonic saline. Animals in hemorrhage groups underwent bleeding of 30% of blood volume. Renal function and renal histology were then evaluated. Plc/H showed the highest serum levels of cytokines, suggesting that pretreatment with parecoxib reduced the inflammatory response in rats subjected to hemorrhage. No difference in tissue cytokine levels between groups was observed. Plc/H showed higher percentage of tubular dilation and degeneration, indicating that parecoxib inhibited tubular injury resulting from renal hypoperfusion. Our findings indicate that pretreatment with a single dose of parecoxib reduced the inflammatory response and tubular renal injury without altering renal function in rats undergoing acute hemorrhage.

  1. Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain

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    Gui-Lin Jin

    2018-01-01

    Full Text Available Despite decades of studies, the currently available drugs largely fail to control neuropathic pain. Koumine—an alkaloidal constituent derived from the medicinal plant Gelsemium elegans Benth.—has been shown to possess analgesic and anti-inflammatory properties; however, the underlying mechanisms remain unclear. In this study, we aimed to investigate the analgesic and anti-inflammatory effects and the possible underlying mechanisms of koumine. The analgesic and anti-inflammatory effects of koumine were explored by using chronic constriction injury of the sciatic nerve (CCI neuropathic pain model in vivo and LPS-induced injury in microglia BV2 cells in vitro. Immunofluorescence staining and Western blot analysis were used to assess the modulator effect of koumine on microglia and astrocyte activation after CCI surgery. Enzyme-linked immunosorbent assay (ELISA was used to evaluate the levels of proinflammatory cytokines. Western blot analysis and quantitative real-time polymerase chain reaction (qPCR were used to examine the modulator effect of koumine on microglial M1 polarization. We found that single or repeated treatment of koumine can significantly reduce neuropathic pain after nerve injury. Moreover, koumine showed inhibitory effects on CCI-evoked microglia and astrocyte activation and reduced proinflammatory cytokine production in the spinal cord in rat CCI models. In BV2 cells, koumine significantly inhibited microglia M1 polarization. Furthermore, the analgesic effect of koumine was inhibited by a TSPO antagonist PK11195. These findings suggest that the analgesic effects of koumine on CCI-induced neuropathic pain may result from the inhibition of microglia activation and M1 polarization as well as the activation of astrocytes while sparing the anti-inflammatory responses to neuropathic pain.

  2. Late-Onset Inflammatory Response to Hyaluronic Acid Dermal Fillers

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    Tahera Bhojani-Lynch, MRCOphth, CertLRS, MBCAM, DipCS

    2017-12-01

    Conclusion:. Late-onset inflammatory reactions to HA fillers may be self-limiting but are easily and rapidly treatable with oral steroids, and with hyaluronidase in the case of lumps. It is likely these reactions are due to a Type IV delayed hypersensitivity response. Delayed inflammation associated with HA fillers is nonbrand specific. However, the case where 2 different brands were injected during the same session, but only 1 brand triggered a hypersensitivity reaction, suggests that the technology used in the manufacturing process, and the subsequent differing products of degradation, may have an influence on potential allergic reactions to HA fillers.

  3. Cytokine balance in human malaria: does Plasmodium vivax elicit more inflammatory responses than Plasmodium falciparum?

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    Raquel M Gonçalves

    Full Text Available BACKGROUND: The mechanisms by which humans regulate pro- and anti-inflammatory responses on exposure to different malaria parasites remains unclear. Although Plasmodium vivax usually causes a relatively benign disease, this parasite has been suggested to elicit more host inflammation per parasitized red blood cell than P. falciparum. METHODOLOGY/PRINCIPAL FINDINGS: We measured plasma concentrations of seven cytokines and two soluble tumor necrosis factor (TNF-α receptors, and evaluated clinical and laboratory outcomes, in Brazilians with acute uncomplicated infections with P. vivax (n = 85, P. falciparum (n = 30, or both species (n = 12, and in 45 asymptomatic carriers of low-density P. vivax infection. Symptomatic vivax malaria patients, compared to those infected with P. falciparum or both species, had more intense paroxysms, but they had no clear association with a pro-inflammatory imbalance. To the contrary, these patients had higher levels of the regulatory cytokine interleukin (IL-10, which correlated positively with parasite density, and elevated IL-10/TNF-α, IL-10/interferon (IFN-γ, IL-10/IL-6 and sTNFRII/TNF-α ratios, compared to falciparum or mixed-species malaria patient groups. Vivax malaria patients had the highest levels of circulating soluble TNF-α receptor sTNFRII. Levels of regulatory cytokines returned to normal values 28 days after P. vivax clearance following chemotherapy. Finally, asymptomatic carriers of low P. vivax parasitemias had substantially lower levels of both inflammatory and regulatory cytokines than did patients with clinical malaria due to either species. CONCLUSIONS: Controlling fast-multiplying P. falciparum blood stages requires a strong inflammatory response to prevent fulminant infections, while reducing inflammation-related tissue damage with early regulatory cytokine responses may be a more cost-effective strategy in infections with the less virulent P. vivax parasite. The early induction

  4. The tripeptide feG ameliorates systemic inflammatory responses to rat intestinal anaphylaxis

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    Davison Joseph S

    2002-08-01

    Full Text Available Abstract Background Food allergies are generally associated with gastrointestinal upset, but in many patients systemic reactions occur. However, the systemic effects of food allergies are poorly understood in experimental animals, which also offer the opportunity to explore the actions of anti-allergic drugs. The tripeptide D-phenylalanine-D-glutamate-Glycine (feG, which potentially alleviates the symptoms of systemic anaphylactic reactions, was tested to determine if it also reduced systemic inflammatory responses provoked by a gastric allergic reaction. Results Optimal inhibition of intestinal anaphylaxis was obtained when 100 μg/kg of feG was given 20 min before the rats were challenged with antigen. The increase in total circulating neutrophils and accumulation of neutrophils in the heart, developing 3 h and 24 h, respectively, after antigen challenge were reduced by both feG and dexamethasone. Both anti-inflammatory agents reduced the increase in vascular permeability induced by antigen in the intestine and the peripheral skin (pinna, albeit with different time courses. Dexamethasone prevented increases in vascular permeability when given 12 h before antigen challenge, whereas feG was effective when given 20 min before ingestion of antigen. The tripeptide prevented the anaphylaxis induced up regulation of specific antibody binding of a cell adhesion molecule related to neutrophil activation, namely CD49d (α4 integrin. Conclusions Aside from showing that intestinal anaphylaxis produces significant systemic inflammatory responses in non-intestinal tissues, our results indicate that the tripeptide feG is a potent inhibitor of extra-gastrointestinal allergic reactions preventing both acute (30 min and chronic (3 h or greater inflammatory responses.

  5. Identification of health problems in patients with acute inflammatory arthritis, using the International Classification of Functioning, Disability and Health (ICF).

    Science.gov (United States)

    Zochling, J; Grill, E; Scheuringer, M; Liman, W; Stucki, G; Braun, J

    2006-01-01

    To identify the most common health problems experienced by patients with acute inflammatory arthritis using the International Classification of Functioning, Disability and Health (ICF), and to provide empirical data for the development of an ICF Core Set for acute inflammatory arthritis. Cross-sectional survey of patients with acute inflammatory arthritis of two or more joints requiring admission to an acute hospital. The second level categories of the ICF were used to collect information on patients' health problems. Relative frequencies of impairments, limitations and restrictions in the study population were reported for the ICF components Body Functions, Body Structures, and Activities and Participations. For the component Environmental Factors absolute and relative frequencies of perceived barriers or facilitators were reported. In total, 130 patients were included in the survey. The mean age of the population was 59.9 years (median age 63.0 years), 75% of the patients were female. Most had rheumatoid arthritis (57%) or early inflammatory polyarthritis (22%). Fifty-four second-level ICF categories had a prevalence of 30% or more: 3 (8%) belonged to the component Body Structures and 10 (13%) to the component Body Functions. Most categories were identified in the components Activities and Participation (19; 23%) and Environmental Factors (22; 56%). Patients with acute inflammatory arthritis can be well described by ICF categories and components. This study is the first step towards the development of an ICF Core Set for patients with acute inflammatory arthritis.

  6. Role of CC chemokines (macrophage inflammatory protein-1 beta, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Bless, N M; Huber-Lang, M; Guo, R F

    2000-01-01

    The role of the CC chemokines, macrophage inflammatory protein-1 beta (MIP-1 beta), monocyte chemotactic peptide-1 (MCP-1), and RANTES, in acute lung inflammatory injury induced by intrapulmonary deposition of IgG immune complexes injury in rats was determined. Rat MIP-1 beta, MCP-1, and RANTES w...

  7. Type 2 diabetes mellitus with early phase acute inflammatory protein on serum protein electrophoresis

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    ET Tuladhar

    2012-03-01

    Full Text Available Background: The onset of Type 2 diabetes has been associated with low grade systemic inflammation. The inflammatory status has been studied by measuring acute phase reactant proteins like hsCRP, α1- antitrypsin, α1-acid glycoprotein, ceruloplasmin, fibrinogen. Most of these acute phase reactants form α1 and α2 bands on electropherogram of serum proteins. The aim of this study was to evaluate inflammatory status in controlled and uncontrolled type 2 diabetes using cellulose acetate electrophoresis and to find the impact of glycemic status as indicated by HbA1c on inflammation process. Materials and Methods: Serum protein electrophoresis was done on serum samples of 60 cases of Diabetes [controlled and uncontrolled] using cellulose acetate paper technique. The electropherogram obtained was stained with Ponseu S and then quantitated using densitometer. Glycemic status was studied by HbA1c analysis. The density of α1and α2 bands in electropherogram were correlated with HbA1c level. Result: A significant increase in the percentage of α1 and α2 band proteins (0.765 and 0.716, p<0.001 were found with the increasing level of HbA1c. With cutoff of HbA1c 7% (American Diabetic Association recommended, the α1 and α2 serum proteins concentration are significantly higher (p<0.001 in uncontrolled diabetes mellitus compared to controlled diabetes mellitus Conclusion: Cellulose acetate electrophoresis of serum proteins show early phase acute inflammatory status in uncontrolled type 2 diabetes mellitus. The process of systemic inflammation worsens with uncontrolled glycemia as indicated by HbA1c. Inflammatory status should be studied adjunct to glycemic status. DOI: http://dx.doi.org/10.3126/jpn.v2i3.6024 JPN 2012; 2(3: 211-214

  8. Short communication: Camel milk ameliorates inflammatory responses and oxidative stress and downregulates mitogen-activated protein kinase signaling pathways in lipopolysaccharide-induced acute respiratory distress syndrome in rats.

    Science.gov (United States)

    Zhu, Wei-Wei; Kong, Gui-Qing; Ma, Ming-Ming; Li, Yan; Huang, Xiao; Wang, Li-Peng; Peng, Zhen-Yi; Zhang, Xiao-Hua; Liu, Xiang-Yong; Wang, Xiao-Zhi

    2016-01-01

    Acute respiratory distress syndrome (ARDS) is a complex syndrome disorder with high mortality rate. Camel milk (CM) contains antiinflammatory and antioxidant properties and protects against numerous diseases. This study aimed to demonstrate the function of CM in lipopolysaccharide (LPS)-induced ARDS in rats. Camel milk reduced the lung wet:dry weight ratio and significantly reduced LPS-induced increases in neutrophil infiltration, interstitial and intra-alveolar edema, thickness of the alveolar wall, and lung injury scores of lung tissues. It also had antiinflammatory and antioxidant effects on LPS-induced ARDS. After LPS stimulation, the levels of proinflammatory cytokines (tumor necrosis factor-α, IL-10, and IL-1β) in serum and oxidative stress markers (malondialdehyde, myeloperoxidase, and total antioxidant capacity) in lung tissue were notably attenuated by CM. Camel milk also downregulated mitogen-activated protein kinase signaling pathways. Given these results, CM is a potential complementary food for ARDS treatment. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  9. The mathematical pathogenetic factors analysis of acute inflammatory diseases development of bronchopulmonary system among infants

    Directory of Open Access Journals (Sweden)

    G. O. Lezhenko

    2017-10-01

    Full Text Available The purpose. To study the factor structure and to establish the associative interaction of pathogenetic links of acute diseases development of the bronchopulmonary system in infants.Materials and methods. The examination group consisted of 59 infants (average age 13.8 ± 1.4 months sick with acute inflammatory bronchopulmonary diseases. Also we tested the level of 25-hydroxyvitamin D (25(ОНD, vitamin D-binding protein, hBPI, cathelicidin LL-37, ß1-defensins, lactoferrin in blood serum with the help of immunoenzymometric analysis. Selection of prognostically important pathogenetic factors of acute bronchopulmonary disease among infants was conducted using ROC-analysis. The procedure for classifying objects was carried out using Hierarchical Cluster Analysis by the method of Centroid-based clustering. Results. Based on the results of the ROC-analysis were selected 15 potential predictors of the development of acute inflammatory diseases of the bronchopulmonary system among infants. The factor analysis made it possible to determine the 6 main components . The biggest influence in the development of the disease was made by "the anemia factor", "the factor of inflammation", "the maternal factor", "the vitamin D supply factor", "the immune factor" and "the phosphorus-calcium exchange factor” with a factor load of more than 0.6. The performed procedure of hierarchical cluster analysis confirmed the initial role of immuno-inflammatory components. The conclusions. The highlighted factors allowed to define a group of parameters, that must be influenced to achieve a maximum effect in carrying out preventive and therapeutic measures. First of all, it is necessary to influence the "the anemia factor" and "the calcium exchange factor", as well as the "the vitamin D supply factor". In other words, to correct vitamin D deficiency and carry out measures aimed at preventing the development of anemia. The prevention and treatment of the pathological course of

  10. Inhibition of the activity of pro-inflammatory secretory phospholipase A2 by acute phase proteins

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    W. Pruzanski

    1996-01-01

    Full Text Available Pro-Inflammatory non-pancreatic phospholipase A2 (sPLA2 is markedly over-expressed in acute systemic and chronic local inflammatory processes. Since in acute phase reaction sPLA2 is often over-expressed simultaneously with acute phase proteins (APP, it is important to determine whether APP interacts with sPLA2. We tested ten APPs for interaction with sPLA2 using as a substrate multilamellar Hposomes composed either of PC:Lyso PC or PE:Lyso PE. Using PC:Lyso PC substrate, CRP, lactoferrin and SAP were found to inhibit sPLA2 activity with an IC50 of 25 μg/ml, 7.5 μg/ml and 50 μg/ml, respectively, corresponding to 0.21 μM, 0.1 μM and 0.21 μM respectively. Using PE:Lyso PE substrate only SAP was inhibitory, with an IC50 of 10 μg/ml (0.04 μM. Phosphorylcholine abolished the inhibitory activity of CRP but not of SAP or lactoferrin. Addition of phosphorylethanolamine or of excess calcium had no effect on the inhibitory activity of APP. Limulin, lysozyme, transferrin, β2-microglobulin, α2-macroglobulin, human and bovine albumins had no effect on sPLA2 activity. Therefore neither the structure of pentraxins, or ironbinding, bacteriostatic property or amyloidogenic property preclude whether APP modulates sPLA2 activity. Inhibition of pro-inflammatory sPLA2 by APP may be one of the protective mechanisms of the acute phase reaction.

  11. Airway Humidification Reduces the Inflammatory Response During Mechanical Ventilation.

    Science.gov (United States)

    Jiang, Min; Song, Jun-Jie; Guo, Xiao-Li; Tang, Yong-Lin; Li, Hai-Bo

    2015-12-01

    Currently, no clinical or animal studies have been performed to establish the relationship between airway humidification and mechanical ventilation-induced lung inflammatory responses. Therefore, an animal model was established to better define this relationship. Rabbits (n = 40) were randomly divided into 6 groups: control animals, sacrificed immediately after anesthesia (n = 2); dry gas group animals, subjected to mechanical ventilation for 8 h without humidification (n = 6); and experimental animals, subjected to mechanical ventilation for 8 h under humidification at 30, 35, 40, and 45°C, respectively (n = 8). Inflammatory cytokines in the bronchi alveolar lavage fluid (BALF) were measured. The integrity of the airway cilia and the tracheal epithelium was examined by scanning and transmission electron microscopy, respectively. Peripheral blood white blood cell counts and the wet to dry ratio and lung pathology were determined. Dry gas group animals showed increased tumor necrosis factor alpha levels in BALF compared with control animals (P humidification temperature was increased to 40°C. Scanning and transmission electron microscopy analysis revealed that cilia integrity was maintained in the 40°C groups. Peripheral white blood cell counts were not different among those groups. Compared with control animals, the wet to dry ratio was significantly elevated in the dry gas group (P humidification at 40°C resulted in reduced pathologic injury compared with the other groups based on the histologic score. Pathology and reduced inflammation observed in animals treated at 40°C was similar to that observed in the control animals, suggesting that appropriate humidification reduced inflammatory responses elicited as a consequence of mechanical ventilation, in addition to reducing damage to the cilia and reducing water loss in the airway. Copyright © 2015 by Daedalus Enterprises.

  12. Pro-inflammatory genetic profile and familiarity of acute myocardial infarction.

    Science.gov (United States)

    Ianni, Manuela; Callegari, Sergio; Rizzo, Antonio; Pastori, Paolo; Moruzzi, Paolo; Corradi, Domenico; Porcellini, Elisa; Campo, Gianluca; Ferrari, Roberto; Ferrario, Marco M; Bitonte, Stefania; Carbone, Ilaria; Licastro, Federico

    2012-06-24

    Acute myocardial infarction (AMI) is a multifactorial disease with a complex pathogenesis where lifestyle, individual genetic background and environmental risk factors are involved. Altered inflammatory responses are implicated in the pathogenesis of atherosclerosis and a premature AMI of parents is associated with an increased risk of the disease in their offspring (Offs). However, the genetic background of familiarity for AMI is still largely unknown. To understand which genes may predispose to increased risk of cardiovascular disease gene polymorphism of immune regulatory genes, and clinical events from the Offs of parents with an early AMI were investigated. Genetics data from Offs were compared with those obtained from healthy subjects and an independent cohort of patients with clinical sporadic AMI. Rates of clinical events during a 24 years follow up from Offs and from an independent Italian population survey were also evaluated. This study showed that a genetic signature consisting of the concomitant presence of the CC genotype of VEGF, the A allele of IL-10 and the A allele of IFN-γ was indeed present in the Offs population. In fact, the above genetic markers were more frequent in unaffected Offs (46.4%) and patients with sporadic AMI (31.8%) than in the CTR (17.3%) and the differences were highly statistically significant (Offs vs CTR: p = 0.0001, OR = 4.129; AMI vs CTR: p = 0.0001, OR = 2.224). During the 24-year follow-up, Offs with a positive familiarity in spite of a relatively young age showed an increased prevalence of diabetes, ischemic heart disease and stroke. These findings reinforce the notion that subjects with a familial history of AMI are at risk of an accelerated aging of cardiovascular system resulting in cardiovascular events. Our data suggest that selected genes with immune regulatory functions are part of the complex genetic background contributing to familiarity for cardiovascular diseases. This inflammatory genetic

  13. Pro-inflammatory genetic profile and familiarity of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Ianni Manuela

    2012-06-01

    Full Text Available Abstract Background Acute myocardial infarction (AMI is a multifactorial disease with a complex pathogenesis where lifestyle, individual genetic background and environmental risk factors are involved. Altered inflammatory responses are implicated in the pathogenesis of atherosclerosis and a premature AMI of parents is associated with an increased risk of the disease in their offspring (Offs. However, the genetic background of familiarity for AMI is still largely unknown. To understand which genes may predispose to increased risk of cardiovascular disease gene polymorphism of immune regulatory genes, and clinical events from the Offs of parents with an early AMI were investigated. Genetics data from Offs were compared with those obtained from healthy subjects and an independent cohort of patients with clinical sporadic AMI. Rates of clinical events during a 24 years follow up from Offs and from an independent Italian population survey were also evaluated. Results This study showed that a genetic signature consisting of the concomitant presence of the CC genotype of VEGF, the A allele of IL-10 and the A allele of IFN-γ was indeed present in the Offs population. In fact, the above genetic markers were more frequent in unaffected Offs (46.4% and patients with sporadic AMI (31.8% than in the CTR (17.3% and the differences were highly statistically significant (Offs vs CTR: p = 0.0001, OR = 4.129; AMI vs CTR: p = 0.0001, OR = 2.224. During the 24-year follow-up, Offs with a positive familiarity in spite of a relatively young age showed an increased prevalence of diabetes, ischemic heart disease and stroke. These findings reinforce the notion that subjects with a familial history of AMI are at risk of an accelerated aging of cardiovascular system resulting in cardiovascular events. Conclusion Our data suggest that selected genes with immune regulatory functions are part of the complex genetic background contributing to familiarity

  14. An Unbalanced Inflammatory Cytokine Response Is Not Associated With Mortality Following Sepsis: A Prospective Cohort Study

    NARCIS (Netherlands)

    Frencken, Jos F.; van Vught, Lonneke A.; Peelen, Linda M.; Ong, David S. Y.; Klein Klouwenberg, Peter M. C.; Horn, Janneke; Bonten, Marc J. M.; van der Poll, Tom; Cremer, Olaf L.; de Beer, Friso M.; Bos, Lieuwe D. J.; Glas, Gerie J.; van Hooijdonk, Roosmarijn T. M.; Hoogendijk, Arie J.; Huson, Mischa A.; Schouten, Laura R. A.; Straat, Marleen; Witteveen, Esther; Wieske, Luuk

    2017-01-01

    The prevailing theory of host response during sepsis states that an excessive production of pro-inflammatory mediators causes early deaths, whereas a predominantly anti-inflammatory response may lead to immunosuppression, secondary infection, and late deaths. We assessed inflammatory (im)balance by

  15. Detection of Hyperechoic Inflammatory Fatty Tissue during Transabdominal Ultrasonography: Diagnostic Role in Acute Abdomen

    International Nuclear Information System (INIS)

    Park, Seong Jin; Lee, Hae Kyung; Yi, Bum Ha; Kim, Hyun Cheol

    2005-01-01

    To assess the incidence and diagnostic role of hyperechoic inflammatory fatty tissue (HIFT) in transabdominal ultrasonography (TAUS) for acute abdomen. With TAUS, we examined 98 consecutive patients (68 women, 30 men: mean age, 32 years: age range, 4-84 years) having acute abdominal pain. We examined the abdomen and pelvis by TAUS to determine the cause of acute abdomen, to check for the presence of HIFT, and to investigate whether it was easier and earlier to find the main cause and HIFT presence. We also prospectively evaluated the shape, distribution, and diagnostic role of HIFT. Final diagnoses consisted of 47 cases of acute appendicitis, 14 of enterocolitis, 13 of PID, 7 of gynecological hemoperitoneum, 5 of colonic diverticulitis, 3 of ovarian torsion, 2 of colon perforation, 2 of only presence of non-specific HIFT, 1 of mesenteric lymphadenitis, and 4 of normal. HIFT were seen in 67 patients (68.4%), including 44/47(93.6%) of acute appendicitis, 2/14(14.3%) of enterocolitis, 11/13(84.6%) of PID, 0/7 of hemoperitoneum, 5/5 of colonic diverticulitis, 0/3 of ovarian torsion, 2/2 of colon perforation, and 1/1 mesenteric lymphadenitis. HIFT were detected earlier than the main cause in 17/44 of acute appendicitis, 6/11 of PID, and 4/5 of colonic diverticulitis. In acute appendicitis, the shape of HIFT appeared as fat thickening along the mesoappendix in 12/44, fat thickening along the mesoappendix and the opposite side in 13/44, fat encircled appendix in 6/44, fatty mass wrapping abscess in 10/44, and diffuse intraperitoneal fat thickening in 3/44. In PID, HIFT appeared as a single fatty mass in the pelvis and lower abdomen in 6/11, wrapping pelvic abscess in 2/11, and multiple fatty masses scattered in abdomen and pelvis in 3/11. In colonic diverticulitis, all 5 cases appeared as hyperechoic hemispheric mass covering the inflamed diverticulum. HIFT are a usual US finding in patients with acute abdomen, particularly on abdominal and pelvic inflammatory conditions

  16. Detection of Hyperechoic Inflammatory Fatty Tissue during Transabdominal Ultrasonography: Diagnostic Role in Acute Abdomen

    Energy Technology Data Exchange (ETDEWEB)

    Park, Seong Jin; Lee, Hae Kyung; Yi, Bum Ha [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Kim, Hyun Cheol [Soonchunhyang University Cheonan Hospital, Cheonan (Korea, Republic of)

    2005-12-15

    To assess the incidence and diagnostic role of hyperechoic inflammatory fatty tissue (HIFT) in transabdominal ultrasonography (TAUS) for acute abdomen. With TAUS, we examined 98 consecutive patients (68 women, 30 men: mean age, 32 years: age range, 4-84 years) having acute abdominal pain. We examined the abdomen and pelvis by TAUS to determine the cause of acute abdomen, to check for the presence of HIFT, and to investigate whether it was easier and earlier to find the main cause and HIFT presence. We also prospectively evaluated the shape, distribution, and diagnostic role of HIFT. Final diagnoses consisted of 47 cases of acute appendicitis, 14 of enterocolitis, 13 of PID, 7 of gynecological hemoperitoneum, 5 of colonic diverticulitis, 3 of ovarian torsion, 2 of colon perforation, 2 of only presence of non-specific HIFT, 1 of mesenteric lymphadenitis, and 4 of normal. HIFT were seen in 67 patients (68.4%), including 44/47(93.6%) of acute appendicitis, 2/14(14.3%) of enterocolitis, 11/13(84.6%) of PID, 0/7 of hemoperitoneum, 5/5 of colonic diverticulitis, 0/3 of ovarian torsion, 2/2 of colon perforation, and 1/1 mesenteric lymphadenitis. HIFT were detected earlier than the main cause in 17/44 of acute appendicitis, 6/11 of PID, and 4/5 of colonic diverticulitis. In acute appendicitis, the shape of HIFT appeared as fat thickening along the mesoappendix in 12/44, fat thickening along the mesoappendix and the opposite side in 13/44, fat encircled appendix in 6/44, fatty mass wrapping abscess in 10/44, and diffuse intraperitoneal fat thickening in 3/44. In PID, HIFT appeared as a single fatty mass in the pelvis and lower abdomen in 6/11, wrapping pelvic abscess in 2/11, and multiple fatty masses scattered in abdomen and pelvis in 3/11. In colonic diverticulitis, all 5 cases appeared as hyperechoic hemispheric mass covering the inflamed diverticulum. HIFT are a usual US finding in patients with acute abdomen, particularly on abdominal and pelvic inflammatory conditions

  17. Inflammatory and Bone Remodeling Responses to the Cytolethal Distending Toxins

    Directory of Open Access Journals (Sweden)

    Georgios N. Belibasakis

    2014-04-01

    Full Text Available The cytolethal distending toxins (CDTs are a family of exotoxins produced by a wide range of Gram-negative bacteria. They are known for causing genotoxic stress to the cell, resulting in growth arrest and eventually apoptotic cell death. Nevertheless, there is evidence that CDTs can also perturb the innate immune responses, by regulating inflammatory cytokine production and molecular mediators of bone remodeling in various cell types. These cellular and molecular events may in turn have an effect in enhancing local inflammation in diseases where CDT-producing bacteria are involved, such as Aggregatibacter actinomycetemcomitans, Haemophilus ducreyi, Campylobacter jejuni and Helicobacter hepaticus. One special example is the induction of pathological bone destruction in periodontitis. The opportunistic oral pathogen Aggregatibatcer actinoycemetemcomitans, which is involved in the aggressive form of the disease, can regulate the molecular mechanisms of bone remodeling in a manner that favors bone resorption, with the potential involvement of its CDT. The present review provides an overview of all known to-date inflammatory or bone remodeling responses of CDTs produced by various bacterial species, and discusses their potential contribution to the pathogenesis of the associated diseases.

  18. Postoperative fever: a normal inflammatory response or cause for concern.

    Science.gov (United States)

    Burke, Lindsay

    2010-04-01

    To devise a systematic diagnostic strategy displayed in algorithm format to assist advanced practice registered nurses (APRNs) in determining when postoperative fever is simply a normal inflammatory response and when further investigation is needed to rule out infection or other serious noninfectious causes of fever. Selected research and clinical articles. Postoperative fever is often a normal inflammatory response to surgery, but it can also be a manifestation of a serious underlying infectious or noninfectious etiology. Therefore, it is important to approach each instance of postoperative fever in a systematic manner. The role of the APRN in managing surgical patients requires being able to accurately assess and evaluate the cause of postoperative fever and take action accordingly. That means taking into account a variety of factors (e.g., patient's medical history, physical examination findings, and type of surgery), so that appropriate diagnostic tests can be ordered to evaluate the cause of the postoperative fever. By being aware of the causes of postoperative fever, the APRN can also take prophylactic action to decrease the risk associated with many of these potential febrile causes.

  19. Acute injury in the peripheral nervous system triggers an alternative macrophage response

    Directory of Open Access Journals (Sweden)

    Ydens Elke

    2012-07-01

    Full Text Available Abstract Background The activation of the immune system in neurodegeneration has detrimental as well as beneficial effects. Which aspects of this immune response aggravate the neurodegenerative breakdown and which stimulate regeneration remains an open question. To unravel the neuroprotective aspects of the immune system we focused on a model of acute peripheral nerve injury, in which the immune system was shown to be protective. Methods To determine the type of immune response triggered after axotomy of the sciatic nerve, a model for Wallerian degeneration in the peripheral nervous system, we evaluated markers representing the two extremes of a type I and type II immune response (classical vs. alternative using real-time quantitative polymerase chain reaction (RT-qPCR, western blot, and immunohistochemistry. Results Our results showed that acute peripheral nerve injury triggers an anti-inflammatory and immunosuppressive response, rather than a pro-inflammatory response. This was reflected by the complete absence of classical macrophage markers (iNOS, IFNγ, and IL12p40, and the strong up-regulation of tissue repair markers (arginase-1, Ym1, and Trem2. The signal favoring the alternative macrophage environment was induced immediately after nerve damage and appeared to be established within the nerve, well before the infiltration of macrophages. In addition, negative regulators of the innate immune response, as well as the anti-inflammatory cytokine IL-10 were induced. The strict regulation of the immune system dampens the potential tissue damaging effects of an over-activated response. Conclusions We here demonstrate that acute peripheral nerve injury triggers an inherent protective environment by inducing the M2 phenotype of macrophages and the expression of arginase-1. We believe that the M2 phenotype, associated with a sterile inflammatory response and tissue repair, might explain their neuroprotective capacity. As such, shifting the

  20. Immune and inflammatory responses in the CNS : Modulation by astrocytes

    DEFF Research Database (Denmark)

    Penkowa, Milena; aschner, michael; hidalgo, juan

    2008-01-01

    the communication between hematogenous cells and resident cells of the central nervous system (CNS). This review will address (1) the functions of astrocytes in the normal brain and (2) their role in surveying noxious stimuli within the brain, with particular emphasis on astrocytic responses to damage or disease......, a process referred to as reactive astrogliosis/ astrocytosis. In addition, the review will discuss (3) the role of astrocytes as an abundant cellular source for immunoregulatory (cytokines) factors, and their fundamental roles in the type and extent of CNS immune and inflammatory responses. (4) Recent...... experimental evidence on the role of astroglia in the etiology of neurological diseases will be highlighted, along with (5) the role of oxidative stressors generated within astrocytes in this process....

  1. Toxoplasma gondii effectors are master regulators of the inflammatory response

    Science.gov (United States)

    Melo, Mariane B.; Jensen, Kirk D.C.; Saeij, Jeroen P.J.

    2011-01-01

    Toxoplasma is a highly successful parasite that establishes a life-long chronic infection. To do this it must carefully regulate immune activation and host cell effector mechanisms. Here we review the latest developments in our understanding of how Toxoplasma counteracts the host’s immune response, and in some cases provokes it, through the use of specific parasite effector proteins. An emerging theme from these discoveries is that Toxoplasma effectors are master regulators of the pro-inflammatory response, which elicits many of the host’s toxoplasmacidal mechanisms. We speculate that combinations of these effectors present in certain Toxoplasma strains work to maintain an optimal parasite burden in different hosts to ensure parasite transmission. PMID:21893432

  2. Immune and inflammatory responses in the CNS : Modulation by astrocytes

    DEFF Research Database (Denmark)

    Penkowa, Milena; aschner, michael; hidalgo, juan

    2008-01-01

    , a process referred to as reactive astrogliosis/ astrocytosis. In addition, the review will discuss (3) the role of astrocytes as an abundant cellular source for immunoregulatory (cytokines) factors, and their fundamental roles in the type and extent of CNS immune and inflammatory responses. (4) Recent......Beyond their long-recognized support functions, astrocytes are active partners of neurons in processing information, synaptic integration, and production of trophic factors, just to name a few. Both microglia and astrocytes produce and secrete a number of cytokines, modulating and integrating...... the communication between hematogenous cells and resident cells of the central nervous system (CNS). This review will address (1) the functions of astrocytes in the normal brain and (2) their role in surveying noxious stimuli within the brain, with particular emphasis on astrocytic responses to damage or disease...

  3. Early severe inflammatory responses to uropathogenic E. coli predispose to chronic and recurrent urinary tract infection.

    Directory of Open Access Journals (Sweden)

    Thomas J Hannan

    2010-08-01

    Full Text Available Chronic infections are an increasing problem due to the aging population and the increase in antibiotic resistant organisms. Therefore, understanding the host-pathogen interactions that result in chronic infection is of great importance. Here, we investigate the molecular basis of chronic bacterial cystitis. We establish that introduction of uropathogenic E. coli (UPEC into the bladders of C3H mice results in two distinct disease outcomes: resolution of acute infection or development of chronic cystitis lasting months. The incidence of chronic cystitis is both host strain and infectious dose-dependent. Further, development of chronic cystitis is preceded by biomarkers of local and systemic acute inflammation at 24 hours post-infection, including severe pyuria and bladder inflammation with mucosal injury, and a distinct serum cytokine signature consisting of elevated IL-5, IL-6, G-CSF, and the IL-8 analog KC. Mice deficient in TLR4 signaling or lymphocytes lack these innate responses and are resistant, to varying degrees, to developing chronic cystitis. Treatment of C3H mice with the glucocorticoid anti-inflammatory drug dexamethasone prior to UPEC infection also suppresses the development of chronic cystitis. Finally, individuals with a history of chronic cystitis, lasting at least 14 days, are significantly more susceptible to redeveloping severe, chronic cystitis upon bacterial challenge. Thus, we have discovered that the development of chronic cystitis in C3H mice by UPEC is facilitated by severe acute inflammatory responses early in infection, which subsequently are predisposing to recurrent cystitis, an insidious problem in women. Overall, these results have significant implications for our understanding of how early host-pathogen interactions at the mucosal surface determines the fate of disease.

  4. Changing patterns of acute phase proteins and inflammatory mediators in experimental caprine coccidiosis.

    Science.gov (United States)

    Hashemnia, Mohammad; Khodakaram-Tafti, Azizollah; Razavi, Seyed Mostafa; Nazifi, Saeed

    2011-09-01

    This experiment was conducted to assess the changing patterns and relative values of acute phase proteins and inflammatory cytokines in experimental caprine coccidiosis. Eighteen newborn kids were allocated to 3 equal groups. Two groups, A and B, were inoculated with a single dose of 1×10(3) and1×10(5) sporulated oocysts of Eimeria arloingi, respectively. The third group, C, received distilled water as the control. Blood samples were collected from the jugular vein of each kid in both groups before inoculation and at days 7, 14, 21, 28, 35, and 42 post-inoculation (PI), and the levels of haptoglobin (Hp), serum amyloid A (SAA), TNF-α, and IFN-γ were measured. For histopathological examinations, 2 kids were selected from each group, euthanized, and necropsied on day 42 PI. Mean Hp concentrations in groups A and B (0.34 and 0.68 g/L) at day 7 PI were 3.2 and 6.3 times higher than the levels before inoculation. The mean SAA concentrations in groups A and B (25.6 and 83.5 µg/ml) at day 7 PI were 4.2 and 13.7 times higher than the levels before inoculation. The magnitude and duration of the Hp and SAA responses correlated well with the inoculation doses and the severity of the clinical signs and diarrhea in kids. These results were consistent with the histopathological features, which showed advanced widespread lesions in group B. In both groups, significant correlations were observed for TNF-α and IFN-γ with SAA and Hp, respectively. In conclusion, Hp and SAA can be useful non-specific diagnostic indicators in caprine coccidiosis.

  5. Iodinated contrast media alter immune responses in pro-inflammatory states.

    LENUS (Irish Health Repository)

    O'Donnell, David H

    2010-07-01

    Hypertonic saline causes a transient elevation of blood osmolality and has been shown to alter cellular inflammatory responses in pro-inflammatory states. Intravascular administration of iodine contrast media also causes a transient elevation of blood osmolarity.

  6. Innate immune response to pulmonary contusion: identification of cell type-specific inflammatory responses.

    Science.gov (United States)

    Hoth, J Jason; Wells, Jonathan D; Yoza, Barbara K; McCall, Charles E

    2012-04-01

    Lung injury from pulmonary contusion is a common traumatic injury, predominantly seen after blunt chest trauma, such as in vehicular accidents. The local and systemic inflammatory response to injury includes activation of innate immune receptors, elaboration of a variety of inflammatory mediators, and recruitment of inflammatory cells to the injured lung. Using a mouse model of pulmonary contusion, we had previously shown that innate immune Toll-like receptors 2 and 4 (TLR2 and TLR4) mediate the inflammatory response to lung injury. In this study, we used chimeric mice generated by adoptive bone marrow transfer between TLR2 or TLR4 and wild-type mice. We found that, in the lung, both bone marrow-derived and nonmyeloid cells contribute to TLR-dependent inflammatory responses after injury in a cell type-specific manner. We also show a novel TLR2-dependent injury mechanism that is associated with enhanced airway epithelial cell apoptosis and increased pulmonary FasL and Fas expression in the lungs from injured mice. Thus, in addition to cardiopulmonary physiological dysfunction, cell type-specific TLR and their differential response to injury may provide novel specific targets for management of patients with pulmonary contusion.

  7. Inflammatory bowel disease on the risk of acute pancreatitis: A population-based cohort study.

    Science.gov (United States)

    Chen, Yu-Tso; Su, Jiann-Sheng; Tseng, Chih-Wei; Chen, Chia-Chang; Lin, Cheng-Li; Kao, Chia-Hung

    2016-04-01

    To determine whether inflammatory bowel disease (IBD) influences the risk of acute pancreatitis. We identified 11,909 patients diagnosed with IBD between 2000 and 2010 from Taiwan National Health Insurance Research Database as the study cohort. A comparison cohort comprised 47,636 age-matched patients without IBD. Both cohorts were followed-up until the end of 2010 or until being censored. Cox proportional hazards regression models were used to study the effects of IBD on the risks of acute pancreatitis. The overall incidence of acute pancreatitis was 3.56-fold higher in the study cohort than in the comparison cohort (31.8 vs 8.91 per 10,000 person-years, crude hazard ratio [HR] = 3.56, 95% confidence interval [CI] = 2.96-4.28). After adjustment for age, sex, and comorbidities, namely alcohol-related disease, biliary stone, hypertension, hyperlipidemia, diabetes mellitus, obesity, hepatitis B, hepatitis C, hypertriglyceridemia, cardiovascular diseases, chronic kidney disease, chronic obstructive pulmonary disease, and hypercalcemia, the adjusted HR for acute pancreatitis was 2.93-fold higher (95% CI = 2.40-3.58) in the study cohort than in the comparison cohort. IBD is a risk factor for acute pancreatitis. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  8. Effect of peripheral morphine in a human model of acute inflammatory pain

    DEFF Research Database (Denmark)

    Lillesø, J; Hammer, N A; Pedersen, J L

    2000-01-01

    Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h......, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain....

  9. Effects Of Different PUFA Supplementation On Inflammatory Response Markers In Young Soccer Players

    Directory of Open Access Journals (Sweden)

    Radoman Kristina

    2015-12-01

    Full Text Available Considering the limited knowledge regarding the effects of n-3 and n-6 PUFAs on the inflammatory response during physical activity, we aimed to evaluate the level of pro- and anti-inflammatory cytokines in young soccer players before and after a maximal physical load test at the beginning and end of a two-month training process. The study included 75 young footballers from Football School “Kragujevac,” who were followed during the two-month training programme. The subjects were divided into the following groups: 1 control group (consumed a standard diet; 2 group that consumed fish oil (2500 mg of n-3 PUFAs per day; 3 group that consumed nutritional sunflower oil (2500 mg of n-6 PUFAs daily. The maximal progressive exercise test was performed using a treadmill belt. Venous blood samples were drawn 4 times for the determination of cytokine levels (IL-6 and TNF-α: before and after the exercise load test before the two-month training programme (initial measurement and immediately before and after the exercise load test after the two-month training programme (control measurement. Supplementation with fish oil (n-3 has been associated with reduced levels of IL-6 compared with the initial values. After an acute bout of exercise, n-3 PUFAs did not show a significant effect on inflammatory marker dynamics, whereas n-6 PUFAs slightly stimulated the production of TNF-α.

  10. Role of inflammatory response in liver diseases: Therapeutic strategies.

    Science.gov (United States)

    Del Campo, José A; Gallego, Paloma; Grande, Lourdes

    2018-01-27

    Inflammation and tumorigenesis are tightly linked pathways impacting cancer development. Inflammasomes are key signalling platforms that detect pathogenic microorganisms, including hepatitis C virus (HCV) infection, and sterile stressors (oxidative stress, insulin resistance, lipotoxicity) able to activate pro-inflammatory cytokines interleukin-1β and IL-18. Most of the inflammasome complexes that have been described to date contain a NOD-like receptor sensor molecule. Redox state and autophagy can regulate inflammasome complex and, depending on the conditions, can be either pro- or anti-apoptotic. Acute and chronic liver diseases are cytokine-driven diseases as several proinflammatory cytokines (IL-1α, IL-1β, tumor necrosis factor-alpha, and IL-6) are critically involved in inflammation, steatosis, fibrosis, and cancer development. NLRP3 inflammasome gain of function aggravates liver disease, resulting in severe liver fibrosis and highlighting this pathway in the pathogenesis of non-alcoholic fatty liver disease. On the other hand, HCV infection is the primary catalyst for progressive liver disease and development of liver cancer. It is well established that HCV-induced IL-1β production by hepatic macrophages plays a critical and central process that promotes liver inflammation and disease. In this review, we aim to clarify the role of the inflammasome in the aggravation of liver disease, and how selective blockade of this main pathway may be a useful strategy to delay fibrosis progression in liver diseases.

  11. Soluble factors from Lactobacillus reuteri CRL1098 have anti-inflammatory effects in acute lung injury induced by lipopolysaccharide in mice.

    Directory of Open Access Journals (Sweden)

    Milagros Griet

    Full Text Available We have previously demonstrated that Lactobacillus reuteri CRL1098 soluble factors were able to reduce TNF-α production by human peripheral blood mononuclear cells. The aims of this study were to determine whether L. reuteri CRL1098 soluble factors were able to modulate in vitro the inflammatory response triggered by LPS in murine macrophages, to gain insight into the molecular mechanisms involved in the immunoregulatory effect, and to evaluate in vivo its capacity to exert anti-inflammatory actions in acute lung injury induced by LPS in mice. In vitro assays demonstrated that L. reuteri CRL1098 soluble factors significantly reduced the production of pro-inflammatory mediators (NO, COX-2, and Hsp70 and pro-inflammatory cytokines (TNF-α, and IL-6 caused by the stimulation of macrophages with LPS. NF-kB and PI3K inhibition by L. reuteri CRL1098 soluble factors contributed to these inhibitory effects. Inhibition of PI3K/Akt pathway and the diminished expression of CD14 could be involved in the immunoregulatory effect. In addition, our in vivo data proved that the LPS-induced secretion of the pro-inflammatory cytokines, inflammatory cells recruitment to the airways and inflammatory lung tissue damage were reduced in L. reuteri CRL1098 soluble factors treated mice, providing a new way to reduce excessive pulmonary inflammation.

  12. SOCS Proteins as Regulators of Inflammatory Responses Induced by Bacterial Infections: A Review

    Directory of Open Access Journals (Sweden)

    Skyla A. Duncan

    2017-12-01

    Full Text Available Severe bacterial infections can lead to both acute and chronic inflammatory conditions. Innate immunity is the first defense mechanism employed against invading bacterial pathogens through the recognition of conserved molecular patterns on bacteria by pattern recognition receptors (PRRs, especially the toll-like receptors (TLRs. TLRs recognize distinct pathogen-associated molecular patterns (PAMPs that play a critical role in innate immune responses by inducing the expression of several inflammatory genes. Thus, activation of immune cells is regulated by cytokines that use the Janus kinase/signal transducers and activators of transcription (JAK/STAT signaling pathway and microbial recognition by TLRs. This system is tightly controlled by various endogenous molecules to allow for an appropriately regulated and safe host immune response to infections. Suppressor of cytokine signaling (SOCS family of proteins is one of the central regulators of microbial pathogen-induced signaling of cytokines, principally through the inhibition of the activation of JAK/STAT signaling cascades. This review provides recent knowledge regarding the role of SOCS proteins during bacterial infections, with an emphasis on the mechanisms involved in their induction and regulation of antibacterial immune responses. Furthermore, the implication of SOCS proteins in diverse processes of bacteria to escape host defenses and in the outcome of bacterial infections are discussed, as well as the possibilities offered by these proteins for future targeted antimicrobial therapies.

  13. Biotin deficiency enhances the inflammatory response of human dendritic cells.

    Science.gov (United States)

    Agrawal, Sudhanshu; Agrawal, Anshu; Said, Hamid M

    2016-09-01

    The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.

  14. Strong induction of AIM2 expression in human epidermis in acute and chronic inflammatory skin conditions.

    Science.gov (United States)

    de Koning, Heleen D; Bergboer, Judith G M; van den Bogaard, Ellen H; van Vlijmen-Willems, Ivonne M J J; Rodijk-Olthuis, Diana; Simon, Anna; Zeeuwen, Patrick L J M; Schalkwijk, Joost

    2012-12-01

    Absent in melanoma 2 (AIM2) is a double-stranded DNA receptor, and its activation initiates an interleukin-1 beta processing inflammasome. AIM2 is implicated in host defense against several pathogens, but could hypothetically also contribute to autoinflammatory or autoimmune diseases, such as is the case for NLRP3. Using thoroughly characterised antibodies, we analysed AIM2 expression in human tissues and primary cells. A strong epidermal upregulation of AIM2 protein expression was observed in several acute and chronic inflammatory skin disorders, such as psoriasis, atopic dermatitis, venous ulcera, contact dermatitis, and experimental wounds. We also found AIM2 induction by interferon-gamma in submerged and three-dimensional in vitro models of human epidermis. Our data highlight the dynamics of epidermal AIM2 expression, showing Langerhans cell and melanocyte-restricted expression in normal epidermis but a pronounced induction in subpopulations of epidermal keratinocytes under inflammatory conditions. © 2012 John Wiley & Sons A/S.

  15. Local and Systemic Inflammatory Responses to Experimentally Induced Gingivitis

    Science.gov (United States)

    Leishman, Shaneen J.; Seymour, Gregory J.; Ford, Pauline J.

    2013-01-01

    This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF-α decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-α during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P gingivitis adds to the systemic inflammatory burden of an individual. PMID:24227893

  16. The Role of Protein Arginine Methyltransferases in Inflammatory Responses

    Directory of Open Access Journals (Sweden)

    Ji Hye Kim

    2016-01-01

    Full Text Available Protein arginine methyltransferases (PRMTs mediate the methylation of a number of protein substrates of arginine residues and serve critical functions in many cellular responses, including cancer development, progression, and aggressiveness, T-lymphocyte activation, and hepatic gluconeogenesis. There are nine members of the PRMT family, which are divided into 4 types (types I–IV. Although most PRMTs do not require posttranslational modification (PTM to be activated, fine-tuning modifications, such as interactions between cofactor proteins, subcellular compartmentalization, and regulation of RNA, via micro-RNAs, seem to be required. Inflammation is an essential defense reaction of the body to eliminate harmful stimuli, including damaged cells, irritants, or pathogens. However, chronic inflammation can eventually cause several types of diseases, including some cancers, atherosclerosis, rheumatoid arthritis, and periodontitis. Therefore, inflammation responses should be well modulated. In this review, we briefly discuss the role of PRMTs in the control of inflammation. More specifically, we review the roles of four PRMTs (CARM1, PRMT1, PRMT5, and PRMT6 in modulating inflammation responses, particularly in terms of modulating the transcriptional factors or cofactors related to inflammation. Based on the regulatory roles known so far, we propose that PRMTs should be considered one of the target molecule groups that modulate inflammatory responses.

  17. Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis.

    Science.gov (United States)

    Zhang, Wenyao; Li, Xuezhong; Xu, Tong; Ma, Mengru; Zhang, Yong; Gao, Ming-Qing

    2016-11-15

    Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Pain Relief for Acute Urolithiasis: The Case for Non-Steroidal Anti-Inflammatory Drugs.

    Science.gov (United States)

    Steinberg, Peter L; Chang, Steven L

    2016-07-01

    Pain from renal colic is often severe and incapacitating. Many patients require emergent hospitalization and aggressive analgesia to relieve such discomfort. For many years, the optimal analgesic strategy has been sought to manage such severe pain. One of the mainstays of therapy for acute renal colic is with non-steroidal anti-inflammatory drugs (NSAIDs). This paper reviews the mechanism by which NSAIDs allow pain relief in renal colic, the evidence for their use in this condition, and the use of NSAIDs combined with other agents in renal colic.

  19. TREATMENT OF ACUTE INFLAMMATORY DISEASES ACCOMPANIED BY THROAT IRRITATION AND PAIN

    Directory of Open Access Journals (Sweden)

    M. I. Petrovskaya

    2013-01-01

    Full Text Available Pathogenetically, prescription of local action drugs containing a wide spectrum antiseptic is reasonable for the upper respiratory tract diseases accompanied by throat irritation and pain. It should be noted that such drugs are very popular among parents; however, most of these drugs may have a range of side effects, which considerably complicate their use in children. That is why the right choice of local action drugs for the acute inflammatory diseases accompanied by throat irritation and pain is a guarantee of treatment efficacy and high compliance. This article examines pharmacological qualities of an antiseptic-containing local action drug permitted to use in children over 4 years of age.

  20. Differential intrathecal inflammatory markers in acute optic neuritis and later conversion to multiple sclerosis

    DEFF Research Database (Denmark)

    Olesen, Mads Nikolaj; Soelberg, Kerstin; Nilsson, Anna Christine

    Background: Optic neuritis (ON) is often an early inflammatory, demyelinating event of multiple sclerosis (MS). We proffer that cytokine and chemokine profiles may (a) differ between patients with MS-related ON and those with non-MS-related ON and (b) predict conversion to MS in patients presenting...... ON (pcytokines IL-1β, IL-6 and IL-17 were measurable in CSF and serum, levels did not differ between groups. Conclusions: Levels of CSF TNF-α and IL-10 and CXCL13 differed between acute isolated ON patients who had converted to MS at follow...

  1. Inflammatory response during slow- and fast-twitch muscle regeneration.

    Science.gov (United States)

    Zimowska, Malgorzata; Kasprzycka, Paulina; Bocian, Katarzyna; Delaney, Kamila; Jung, Piotr; Kuchcinska, Kinga; Kaczmarska, Karolina; Gladysz, Daria; Streminska, Wladyslawa; Ciemerych, Maria Anna

    2017-03-01

    Skeletal muscles are characterized by their unique ability to regenerate. Injury of a so-called fast-twitch muscle, extensor digitorum longus (EDL), results in efficient regeneration and reconstruction of the functional tissue. In contrast, slow-twitch muscle (soleus) fails to properly reconstruct and develops fibrosis. This study focuses on soleus and EDL muscle regeneration and associated inflammation. We determined differences in the activity of neutrophils and M1 and M2 macrophages using flow cytometry and differences in the levels of proinflammatory cytokines using Western blotting and immunolocalization at different times after muscle injury. Soleus muscle repair is accompanied by increased and prolonged inflammation, as compared to EDL. The proinflammatory cytokine profile is different in the soleus and ED muscles. Muscle repair efficiency differs by muscle fiber type. The inflammatory response affects the repair efficiency of slow- and fast-twitch muscles. Muscle Nerve 55: 400-409, 2017. © 2016 Wiley Periodicals, Inc.

  2. Inflammatory response in laparoscopic vs. open surgery for gastric cancer

    DEFF Research Database (Denmark)

    Okholm, Cecilie; Goetze, Jens Peter; Svendsen, Lars Bo

    2014-01-01

    lead to an increased susceptibility to complications and morbidity. The aim of this review was to investigate if laparoscopic surgery reduces the immunological response compared to open surgery in gastric cancer. METHODS: We conducted a literature search identifying relevant studies comparing......OBJECTIVE: Laparoscopic surgery may offer advantages compared to open surgery, such as earlier mobilization, less pain and lower post-surgical morbidity. Surgical stress is thought to be associated with the postoperative immunological changes in the body as an impaired immune function, which may...... laparoscopy or laparoscopic-assisted surgery with open gastric surgery. The main outcome was postoperative immunological status defined as surgical stress parameters, including inflammatory cytokines and blood parameters. RESULTS: We identified seven studies that addressed the immunological status in patients...

  3. Incidence of systemic inflammatory response syndrome after endovascular aortic repair

    DEFF Research Database (Denmark)

    De La Motte, L; Vogt, K; Jensen, Leif Panduro

    2011-01-01

    AIM: The aim of this study was to estimate the incidence of the post-implantation syndrome/systemic inflammatory response syndrome (SIRS) after endovascular aortic repair. METHODS: All patients, undergoing elective primary endovascular repair of an asymptomatic infrarenal abdominal aortic aneurysm...... during 2007, were retrospectively evaluated for SIRS within the first 5 postoperative days. The only exclusion-criteria were missing data. SIRS was assessed using the criteria defined by the American College of Chest Physicians and Society of Critical Care Medicine Consensus Conference Committee. RESULTS......: Sixty-six patients were included, 40 (60%) met the SIRS criteria within the first 5 postoperative days (95% of the 40 patients met the criteria within 3 days). We found no significant differences between the SIRS and the non-SIRS group in baseline characteristics or other data including volume...

  4. Morphological features of the inflammatory response in molluscs.

    Science.gov (United States)

    De Vico, G; Carella, F

    2012-12-01

    Over the last few years, there has been a large increase in studying the biology and pathology of molluscs, predominantly in addressing the molecular patterns involved in their immune-mediated and inflammatory responses. Conversely, the literature-based diagnostic criteria concerning the morphology of the above phenomena still involves pathogenetic confusion and conflicting terminology. A comparison of bibliographic resources, such as the Abridged Glossary of Terms Used in Invertebrate Pathology and the National Status manual for molluscan histopathological examination and analysis from the NOAA, have revealed variability in the definitions of superimposable lesions, emphasising the need for further efforts in establishing standard terminology and methodologies in this field of study. This review suggests some possible solutions for overcoming the use of parallel terminologies in diagnosing inflammation in molluscs and also highlights conflicting features requiring further discussion. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. High Spinal Anesthesia Enhances Anti-Inflammatory Responses in Patients Undergoing Coronary Artery Bypass Graft Surgery and Aortic Valve Replacement: Randomized Pilot Study.

    Directory of Open Access Journals (Sweden)

    Trevor W R Lee

    Full Text Available Cardiac surgery induces many physiologic changes including major inflammatory and sympathetic nervous system responses. Here, we conducted a single-centre pilot study to generate hypotheses on the potential immune impact of adding high spinal anaesthesia to general anaesthesia during cardiac surgery in adults. We hypothesized that this strategy, previously shown to blunt the sympathetic response and improve pain management, could reduce the undesirable systemic inflammatory responses caused by cardiac surgery.This prospective randomized unblinded pilot study was conducted on 14 patients undergoing cardiac surgery for coronary artery bypass grafting and/or aortic valve replacement secondary to severe aortic stenosis. The primary outcome measures examined longitudinally were serum pro-inflammatory (IL-6, IL-1b, CCL2, anti-inflammatory (IL-10, TNF-RII, IL-1Ra, acute phase protein (CRP, PTX3 and cardiovascular risk (sST2 biomarkers.The kinetics of pro- and anti-inflammatory biomarker was determined following surgery. All pro-inflammatory and acute phase reactant biomarker responses induced by surgical stress were indistinguishable in intensity and duration between control groups and those who also received high spinal anaesthesia. Conversely, IL-10 levels were markedly elevated in both intensity and duration in the group receiving high spinal anesthesia (p = 0.005.This hypothesis generating pilot study suggests that high spinal anesthesia can alter the net inflammatory response that results from cardiac surgery. In appropriately selected populations, this may add incremental benefit by dampening the net systemic inflammatory response during the week following surgery. Larger population studies, powered to assess immune, physiologic and clinical outcomes in both acute and longer term settings, will be required to better assess potential benefits of incorporating high spinal anesthesia.ClinicalTrials.gov NCT00348920.

  6. Sex differences in the inflammatory response of primary astrocytes to lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Santos-Galindo María

    2011-07-01

    Full Text Available Abstract Background Numerous neurological and psychiatric disorders show sex differences in incidence, age of onset, symptomatology or outcome. Astrocytes, one of the glial cell types of the brain, show sex differences in number, differentiation and function. Since astrocytes are involved in the response of neural tissue to injury and inflammation, these cells may participate in the generation of sex differences in the response of the brain to pathological insults. To explore this hypothesis, we have examined whether male and female astrocytes show a different response to an inflammatory challenge and whether perinatal testosterone influences this response. Methods Cortical astrocyte cultures were prepared from postnatal day 1 (one day after birth male or female CD1 mice pups. In addition, cortical astrocyte cultures were also prepared from female pups that were injected at birth with 100 μg of testosterone propionate or vehicle. Cultures were treated for 5 hours with medium containing lipopolysaccharide (LPS or with control medium. The mRNA levels of IL6, interferon-inducible protein 10 (IP10, TNFα, IL1β, Toll-like receptor 4 (TLR4, steroidogenic acute regulatory protein and translocator protein were assessed by quantitative real-time polymerase chain reaction. Statistical significance was assessed by unpaired t-test or by one-way analysis of variance followed by the Tukey post hoc test. Results The mRNA levels of IL6, TNFα and IL1β after LPS treatment were significantly higher in astrocytes derived from male or androgenized females compared to astrocytes derived from control or vehicle-injected females. In contrast, IP10 mRNA levels after LPS treatment were higher in astrocytes derived from control or vehicle-injected females than in those obtained from males or androgenized females. The different response of male and female astrocytes to LPS was due neither to differences in the basal expression of the inflammatory molecules nor to

  7. The human metapneumovirus matrix protein stimulates the inflammatory immune response in vitro.

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    Audrey Bagnaud-Baule

    Full Text Available Each year, during winter months, human Metapneumovirus (hMPV is associated with epidemics of bronchiolitis resulting in the hospitalization of many infants. Bronchiolitis is an acute illness of the lower respiratory tract with a consequent inflammation of the bronchioles. The rapid onset of inflammation suggests the innate immune response may have a role to play in the pathogenesis of this hMPV infection. Since, the matrix protein is one of the most abundant proteins in the Paramyxoviridae family virion, we hypothesized that the inflammatory modulation observed in hMPV infected patients may be partly associated with the matrix protein (M-hMPV response. By western blot analysis, we detected a soluble form of M-hMPV released from hMPV infected cell as well as from M-hMPV transfected HEK 293T cells suggesting that M-hMPV may be directly in contact with antigen presenting cells (APCs during the course of infection. Moreover, flow cytometry and confocal microscopy allowed determining that M-hMPV was taken up by dendritic cells (moDCs and macrophages inducing their activation. Furthermore, these moDCs enter into a maturation process inducing the secretion of a broad range of inflammatory cytokines when exposed to M-hMPV. Additionally, M-hMPV activated DCs were shown to stimulate IL-2 and IFN-γ production by allogeneic T lymphocytes. This M-hMPV-mediated activation and antigen presentation of APCs may in part explain the marked inflammatory immune response observed in pathology induced by hMPV in patients.

  8. Environmental particulate matter induces murine intestinal inflammatory responses and alters the gut microbiome.

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    Lisa Kish

    Full Text Available Particulate matter (PM is a key pollutant in ambient air that has been associated with negative health conditions in urban environments. The aim of this study was to examine the effects of orally administered PM on the gut microbiome and immune function under normal and inflammatory conditions.Wild-type 129/SvEv mice were gavaged with Ottawa urban PM10 (EHC-93 for 7-14 days and mucosal gene expression analyzed using Ingenuity Pathways software. Intestinal permeability was measured by lactulose/mannitol excretion in urine. At sacrifice, segments of small and large intestine were cultured and cytokine secretion measured. Splenocytes were isolated and incubated with PM10 for measurement of proliferation. Long-term effects of exposure (35 days on intestinal cytokine expression were measured in wild-type and IL-10 deficient (IL-10(-/- mice. Microbial composition of stool samples was assessed using terminal restriction fragment length polymorphism. Short chain fatty acids were measured in caecum.Short-term treatment of wild-type mice with PM10 altered immune gene expression, enhanced pro-inflammatory cytokine secretion in the small intestine, increased gut permeability, and induced hyporesponsiveness in splenocytes. Long-term treatment of wild-type and IL-10(-/- mice increased pro-inflammatory cytokine expression in the colon and altered short chain fatty acid concentrations and microbial composition. IL-10(-/- mice had increased disease as evidenced by enhanced histological damage.Ingestion of airborne particulate matter alters the gut microbiome and induces acute and chronic inflammatory responses in the intestine.

  9. Decreased Inflammatory Responses of Human Lung Epithelial Cells after Ethanol Exposure Are Mimicked by Ethyl Pyruvate

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    B. Relja

    2014-01-01

    Full Text Available Background and Purpose. Leukocyte migration into alveolar space plays a critical role in pulmonary inflammation resulting in lung injury. Acute ethanol (EtOH exposure exerts anti-inflammatory effects. The clinical use of EtOH is critical due to its side effects. Here, we compared effects of EtOH and ethyl pyruvate (EtP on neutrophil adhesion and activation of cultured alveolar epithelial cells (A549. Experimental Approach. Time course and dose-dependent release of interleukin- (IL- 6 and IL-8 from A549 were measured after pretreatment of A549 with EtP (2.5–10 mM, sodium pyruvate (NaP, 10 mM, or EtOH (85–170 mM, and subsequent lipopolysaccharide or IL-1beta stimulation. Neutrophil adhesion to pretreated and stimulated A549 monolayers and CD54 surface expression were determined. Key Results. Treating A549 with EtOH or EtP reduced substantially the cytokine-induced release of IL-8 and IL-6. EtOH and EtP (but not NaP reduced the adhesion of neutrophils to monolayers in a dose- and time-dependent fashion. CD54 expression on A549 decreased after EtOH or EtP treatment before IL-1beta stimulation. Conclusions and Implications. EtP reduces secretory and adhesive potential of lung epithelial cells under inflammatory conditions. These findings suggest EtP as a potential treatment alternative that mimics the anti-inflammatory effects of EtOH in early inflammatory response in lungs.

  10. Allograft Inflammatory Factor-1 Links T-Cell Activation, Interferon Response, and Macrophage Activation in Chronic Kawasaki Disease Arteritis.

    Science.gov (United States)

    Rowley, Anne H; Baker, Susan C; Kim, Kwang-Youn A; Shulman, Stanford T; Yang, Amy; Arrollo, David; DeBerge, Matthew; Han, Shuling; Sibinga, Nicholas E S; Pink, Adam J; Thorp, Edward B

    2017-09-01

    Kawasaki disease (KD) is widely viewed as an acute arteritis. However, our pathologic studies show that chronic coronary arteritis can persist long after disease onset and is closely linked with arterial stenosis. Transcriptome profiling of acute KD arteritis tissues revealed upregulation of T lymphocyte, type I interferon, and allograft inflammatory factor-1 (AIF1) genes. We determined whether these immune responses persist in chronic KD arteritis, and we investigated the role of AIF1 in these responses. Gene expression in chronic KD and childhood control arteries was determined by real-time reverse-transcriptase polymerase chain reaction, and arterial protein expression was determined by immunohistochemistry and immunofluorescence. Allograft inflammatory factor-1 small-interfering ribonucleic acid macrophage treatment was performed to investigate the role of AIF1 in macrophage and T lymphocyte activation. Allograft inflammatory factor-1 protein was highly expressed in stenotic KD arteries and colocalized with the macrophage marker CD68. T lymphocyte and interferon pathway genes were significantly upregulated in chronic KD coronary artery tissues. Alpha interferon-induced macrophage expression of CD80 and major histocompatibility complex class II was dependent on AIF1, and macrophage expression of AIF1 was required for antigen-specific T lymphocyte activation. Allograft inflammatory factor-1, originally identified in posttransplant arterial stenosis, is markedly upregulated in KD stenotic arterial tissues. T lymphocyte and type I interferon responses persist in chronic KD arteritis. Allograft inflammatory factor-1 may play multiple roles linking type I interferon response, macrophage activation, and antigen-specific T lymphocyte activation. These results suggest the likely importance of lymphocyte-myeloid cell cross-talk in the pathogenesis of KD arteritis and can inform selection of new immunotherapies for clinical trials in high-risk KD children.

  11. Eccentric Exercise: Physiological Characteristics and Acute Responses.

    Science.gov (United States)

    Douglas, Jamie; Pearson, Simon; Ross, Angus; McGuigan, Mike

    2017-04-01

    An eccentric contraction involves the active lengthening of muscle under an external load. The molecular and neural mechanisms underpinning eccentric contractions differ from those of concentric and isometric contractions and remain less understood. A number of molecular theories have been put forth to explain the unexplained observations during eccentric contractions that deviate from the predictions of the established theories of muscle contraction. Postulated mechanisms include a strain-induced modulation of actin-myosin interactions at the level of the cross-bridge, the activation of the structural protein titin, and the winding of titin on actin. Accordingly, neural strategies controlling eccentric contractions also differ with a greater, and possibly distinct, cortical activation observed despite an apparently lower activation at the level of the motor unit. The characteristics of eccentric contractions are associated with several acute physiological responses to eccentrically-emphasised exercise. Differences in neuromuscular, metabolic, hormonal and anabolic signalling responses during, and following, an eccentric exercise bout have frequently been observed in comparison to concentric exercise. Subsequently, the high levels of muscular strain with such exercise can induce muscle damage which is rarely observed with other contraction types. The net result of these eccentric contraction characteristics and responses appears to be a novel adaptive signal within the neuromuscular system.

  12. Does serum 25-hydroxyvitamin D decrease during acute-phase response? A systematic review.

    Science.gov (United States)

    Silva, Mariana Costa; Furlanetto, Tania Weber

    2015-02-01

    Low levels of 25-hydroxyvitamin D, or 25(OH)D, are commonly associated with inflammatory diseases. These associations could be due to an increased prevalence of inflammatory diseases in hypovitaminosis D, although reverse causality cannot be excluded. We aimed to systematically review the longitudinal studies that reported serum 25(OH)D during an acute inflammatory response in humans. Using Ovid MEDLINE, EMBASE, and the Cochrane Library, an electronic search of the literature was conducted from database inception until January 2014 by combining the MeSH terms: vitamin D and acute-phase reactants. Other sources for obtaining articles were used as cross-referencing texts. Based on 670 titles and abstracts, 40 articles were selected for full-text review, and 8 of these studies met the final inclusion criteria. In 6 of the reviewed studies, 25(OH)D dropped after the inflammatory insult; this decrease was abrupt in the studies that measured 25(OH)D early after the insult. In 2 studies, there was no change of 25(OH)D during the course of the disease, but baseline levels were measured in both after days of symptoms onset. One study suggested that hemodilution decreased 25(OH)D, with no effect on inflammation. Serum C-reactive protein concentrations were used as inflammatory markers in almost all studies. The metabolic meaning and the functional importance of these changes are unknown. In light of the current evidence, the 25(OH)D measured during acute-phase response should be interpreted with care. Future research, including other markers of vitamin D adequacy, could help to clarify if hypovitaminosis D might be the cause or the consequence of inflammatory diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Francisella tularensis subsp. tularensis induces a unique pulmonary inflammatory response: role of bacterial gene expression in temporal regulation of host defense responses.

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    Kathie-Anne Walters

    Full Text Available Pulmonary exposure to Francisella tularensis is associated with severe lung pathology and a high mortality rate. The lack of induction of classical inflammatory mediators, including IL1-β and TNF-α, during early infection has led to the suggestion that F. tularensis evades detection by host innate immune surveillance and/or actively suppresses inflammation. To gain more insight into the host response to Francisella infection during the acute stage, transcriptomic analysis was performed on lung tissue from mice exposed to virulent (Francisella tularensis ssp tularensis SchuS4. Despite an extensive transcriptional response in the lungs of animals as early as 4 hrs post-exposure, Francisella tularensis was associated with an almost complete lack of induction of immune-related genes during the initial 24 hrs post-exposure. This broad subversion of innate immune responses was particularly evident when compared to the pulmonary inflammatory response induced by other lethal (Yersinia pestis and non-lethal (Legionella pneumophila, Pseudomonas aeruginosa pulmonary infections. However, the unique induction of a subset of inflammation-related genes suggests a role for dysregulation of lymphocyte function and anti-inflammatory pathways in the extreme virulence of Francisella. Subsequent activation of a classical inflammatory response 48 hrs post-exposure was associated with altered abundance of Francisella-specific transcripts, including those associated with bacterial surface components. In summary, virulent Francisella induces a unique pulmonary inflammatory response characterized by temporal regulation of innate immune pathways correlating with altered bacterial gene expression patterns. This study represents the first simultaneous measurement of both host and Francisella transcriptome changes that occur during in vivo infection and identifies potential bacterial virulence factors responsible for regulation of host inflammatory pathways.

  14. Urinary 1-Hydroxypyrene is Associated with Oxidative Stress and Inflammatory Biomarkers in Acute Myocardial Infarction

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    Fernando Freitas

    2014-09-01

    Full Text Available Several studies have associated exposure to environmental pollutants, especially polycyclic aromatic hydrocarbons (PAHs, with the development of cardiovascular diseases. Considering that 1-hydroxypyrene (1-OHP is the major biomarker of exposure to pyrenes, the purpose of this study was to evaluate the potential association between 1-OHP and oxidative stress/inflammatory biomarkers in patients who had suffered an acute myocardial infarction (AMI. After adopting the exclusion criteria, 58 post-infarction patients and 41 controls were sub-divided into smokers and non-smokers. Urinary 1-OHP, hematological and biochemical parameters, oxidative stress biomarkers (MDA, SOD, CAT, GPx and exogenous antioxidants and the inflammatory biomarker (hs-CRP were analyzed. 1-OHP levels were increased in post-infarct patients compared to controls (p < 0.05 and were correlated to MDA (r = 0.426, p < 0.01, CAT (r = 0.474, p < 0.001 and β-carotene (r = −0.309; p < 0.05 in non-smokers. Furthermore, post-infarction patients had elevated hs-CRP, MDA, CAT and GPx levels compared to controls for both smokers and non-smokers. Besides, β-carotene levels and SOD activity were decreased in post-infarction patients. In summary, our findings indicate that the exposure to pyrenes was associated to lipid damage and alterations of endogenous and exogenous antioxidants, demonstrating that PAHs contribute to oxidative stress and are associated to acute myocardial infarction.

  15. Acute systemic inflammatory response after cardiac surgery in ...

    African Journals Online (AJOL)

    Post-operatively, there was significant increased biomarkers level in both groups, albeit not between the groups with a significant negative correlation between the mean change in CRP levels and mechanical ventilation (r=0.548, p=0.002) in the seropositive group (r=0.025, p=0.893). The correlation between pre-operative ...

  16. Attenuation of acute systemic inflammatory response after valve surgery

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    Najah R. Hadi

    2017-09-01

    Keywords montelukast, mitral and aortic valve replacement surgery, ischemia reperfusion injury, interleukin-6, cardiac troponin 1, tumor necrotic factor-alpha, alpha 2 macroglobulin/creatinine, ejection fraction, forced vital capacity (FVC, forced expiratory volume in one second (FEV1, FEV1/FVC ratio

  17. Acute systemic inflammatory response after cardiac surgery in ...

    African Journals Online (AJOL)

    2017-09-03

    Sep 3, 2017 ... pandemic, there have been various concerns about the operative risks, infections and benefits of cardiac surgery in patients infected with HIV, as they are known to al- ready have a compromised immune system, chronic in- flammation and reduced survival.1,2 This led to cardiac surgery departments setting ...

  18. Effect of Insulin Therapy using Hyper-insulinemic Normoglycemic Clamp on Inflammatory Response in Brain Dead Organ Donors.

    Science.gov (United States)

    Aljiffry, M; Hassanain, M; Schricker, T; Shaheen, M; Nouh, T; Lattermann, R; Salman, A; Wykes, L; Metrakos, P

    2016-05-01

    Brain death is a major stress that is associated with a massive inflammatory response and systemic hyperglycemia. Severe inflammation leads to increased graft immunogenicity and risk of graft dysfunction; while acute hyperglycemia aggravates the inflammatory response and increases the risk of morbidity and mortality. Insulin therapy not only controls hyperglycemia but also suppresses inflammation. The present study is to investigate the anti-inflammatory properties and the normoglycemia maintenance of high dose insulin on brain dead organ donors. 15 brain dead organ donors were divided into 2 groups, insulin treated (n=6) and controls (n=9). Insulin was provided for a minimum of 6 h using the hyperinsulinemic normoglycemic clamp technique. The changes of serum cytokines, including IL-6, IL-10, IL-1β, IL-8, TNFα, TGFα and MCP-1, were measured by suspension bead array immunoassay and glucose by a glucose monitor. Compared to controls, insulin treated donors had a significant lower blood glucose 4.8 (4-6.9) vs. 9 (5.6-11.7) mmol/L, pinsulin treated donors compared with those in controls. High dose insulin therapy decreases the concentrations of inflammatory cytokines in brain dead donors and preserves normoglycemia. High dose of insulin may have anti-inflammatory effects in brain dead organ donors and therefore, improve the quality of donor organs and potentially improve outcomes. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Burn size determines the inflammatory and hypermetabolic response.

    Science.gov (United States)

    Jeschke, Marc G; Mlcak, Ronald P; Finnerty, Celeste C; Norbury, William B; Gauglitz, Gerd G; Kulp, Gabriela A; Herndon, David N

    2007-01-01

    Increased burn size leads to increased mortality of burned patients. Whether mortality is due to inflammation, hypermetabolism or other pathophysiologic contributing factors is not entirely determined. The purpose of the present study was to determine in a large prospective clinical trial whether different burn sizes are associated with differences in inflammation, body composition, protein synthesis, or organ function. Pediatric burned patients were divided into four burn size groups: 80% TBSA burn. Demographic and clinical data, hypermetabolism, the inflammatory response, body composition, the muscle protein net balance, serum and urine hormones and proteins, and cardiac function and changes in liver size were determined. One hundred and eighty-nine pediatric patients of similar age and gender distribution were included in the study (80% TBSA burn, n = 21). Patients with larger burns had more operations, a greater incidence of infections and sepsis, and higher mortality rates compared with the other groups (P 80% TBSA group, followed by the 60-79% TBSA burn group (P 80% burns lost the most body weight, lean body mass, muscle protein and bone mineral content (P < 0.05). The urine cortisol concentration was highest in the 80-99% and 60-79% TBSA burn groups, associated with significant myocardial depression and increased change in liver size (P < 0.05). The cytokine profile showed distinct differences in expression of IL-8, TNF, IL-6, IL-12p70, monocyte chemoattractant protein-1 and granulocyte-macrophage colony-stimulating factor (P < 0.05). Morbidity and mortality in burned patients is burn size dependent, starts at a 60% TBSA burn and is due to an increased hypermetabolic and inflammatory reaction, along with impaired cardiac function.

  20. Chemical composition, acute toxicity, antioxidant and anti-inflammatory activities of Moroccan Tetraclinis articulata L.

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    Meryem El Jemli

    2017-07-01

    Full Text Available Hydro-distilled essential oil (EO from the leaves of the western Mediterranean and Moroccan endemic plant Tetraclinis articulata was analyzed by GC/MS and examined for its acute toxicity on mice, in order to establish the safe doses. Furthermore, the anti-Inflammatory activity was evaluated based on carrageenan and trauma induced rats paw edema and the antioxidant potential has been investigated using different methods including DPPH radical-scavenging assay, Trolox equivalent antioxidant capacity (TEAC and Ferric-reducing antioxidant power assay (FRAP. The major identified compounds in GC/MS analysis were bornyl acetate (26.81%, camphor (22.40% and α-pinene (7.16%, with 25 other minor constituents. No mortalities in acute toxicity were observed, indicating that the LD50 of T. articulata essential oil is highest than 5 g/kg. In the anti-inflammatory test based on chemical and mechanical induced trauma, the EO demonstrated an effective reduce swelling by 64.71 ± 9.38% and 69.09 ± 6.02% respectively obtained 6 h after administration at the dose of 200 mg/kg when compared to the control groups. Moreover in the antioxidant testing battery, T. articulata essential oil showed a promising scavenging effect measured by DPPH, TEAC and ferric-reducing power assays with IC50 values of 12.05 ± 0.24 mg/mL, 8.90 ± 0.17 mg/mL and 0.15 ± 0.01 mg/mL respectively. These results suggest that, the EO from the leaves of T. articulata constitutes a valuable source of anti-inflammatory and antioxidant metabolites. These findings argue for the possible integration of this oil in pharmaceutical, cosmetic and food industries.

  1. Chemical composition, acute toxicity, antioxidant and anti-inflammatory activities of Moroccan Tetraclinis articulata L.

    Science.gov (United States)

    El Jemli, Meryem; Kamal, Rabie; Marmouzi, Ilias; Doukkali, Zouhra; Bouidida, El Houcine; Touati, Driss; Nejjari, Rachid; El Guessabi, Lahcen; Cherrah, Yahia; Alaoui, Katim

    2017-07-01

    Hydro-distilled essential oil (EO) from the leaves of the western Mediterranean and Moroccan endemic plant Tetraclinis articulata was analyzed by GC/MS and examined for its acute toxicity on mice, in order to establish the safe doses. Furthermore, the anti-Inflammatory activity was evaluated based on carrageenan and trauma induced rats paw edema and the antioxidant potential has been investigated using different methods including DPPH radical-scavenging assay, Trolox equivalent antioxidant capacity (TEAC) and Ferric-reducing antioxidant power assay (FRAP). The major identified compounds in GC/MS analysis were bornyl acetate (26.81%), camphor (22.40%) and α-pinene (7.16%), with 25 other minor constituents. No mortalities in acute toxicity were observed, indicating that the LD 50 of T. articulata essential oil is highest than 5 g/kg. In the anti-inflammatory test based on chemical and mechanical induced trauma, the EO demonstrated an effective reduce swelling by 64.71 ± 9.38% and 69.09 ± 6.02% respectively obtained 6 h after administration at the dose of 200 mg/kg when compared to the control groups. Moreover in the antioxidant testing battery, T. articulata essential oil showed a promising scavenging effect measured by DPPH, TEAC and ferric-reducing power assays with IC 50 values of 12.05 ± 0.24 mg/mL, 8.90 ± 0.17 mg/mL and 0.15 ± 0.01 mg/mL respectively. These results suggest that, the EO from the leaves of T. articulata constitutes a valuable source of anti-inflammatory and antioxidant metabolites. These findings argue for the possible integration of this oil in pharmaceutical, cosmetic and food industries.

  2. Oral warfarin intake affects skin inflammatory cytokine responses in rats.

    Science.gov (United States)

    Aleksandrov, Aleksandra Popov; Mirkov, Ivana; Zolotarevski, Lidija; Ninkov, Marina; Mileusnic, Dina; Kataranovski, Dragan; Kataranovski, Milena

    2017-09-01

    Warfarin is an anticoagulant used in prevention/prophylaxis of thromboembolism. Besides the effects on coagulation, non-hemorrhagic reactions have also been documented. Although cutaneous reactions were reported in some patients, the impact on skin immunity was not explored. In the present paper, the effect of 30-day oral warfarin intake on skin cytokine responses in rats was analyzed. Increased release of inflammatory cytokines (TNF, IL-1β and IL-10) was noted by skin explants from rats which received warfarin, but without effect on IL-6. No impact on epidermal cell cytokine secretion was seen, except a tendency of an increase of IL-6 response to stimulation with microbial product lipopolysaccharide (LPS). Topical application of contact allergen dinitrochlorobenzene (DNCB) resulted in slight (numerical solely) increase of TNF release by skin explants of warfarin-treated animals, while epidermal cells responded by increased secretion of all four cytokines examined. The data presented provide new information on the potential of oral warfarin to modulate skin innate immune activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Maresin 1 Mitigates Inflammatory Response and Protects Mice from Sepsis

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    Ruidong Li

    2016-01-01

    Full Text Available Sepsis, frequently caused by infection of bacteria, is considered as an uncontrollable systematic inflammation response syndrome (SIRS. Maresin 1 (Mar1 is a new proresolving mediator with potent anti-inflammatory effect in several animal models. However, its effect in sepsis is still not investigated. To address this question, we developed sepsis model in BALB/c mice by cecal ligation and puncture (CLP with or without Mar1 treatment. Our data showed that Mar1 markedly improved survival rate and decreased the levels of proinflammatory cytokines in CLP mice such as interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and interleukin-1β (IL-1β. Furthermore, Mar1 reduced serum level of lipopolysaccharide (LPS and enhanced the bacteria clearance in mice sepsis model. Moreover, Mar1 attenuated lung injury and decreased level of alanine transaminase (ALT, aspartate transaminase (AST, creatinine (Cre, and blood urea nitrogen (BUN in serum in mice after CLP surgery. Treatment with Mar1 inhibited activation of nuclear factor kappa B (NF-κb pathway. In conclusion, Mar1 exhibited protective effect in sepsis by reducing LPS, bacteria burden in serum, inhibiting inflammation response, and improving vital organ function. The possible mechanism is partly involved in inhibition of NF-κb activation.

  4. Inflammatory cell response to calcium phosphate biomaterial particles: an overview.

    Science.gov (United States)

    Velard, Frédéric; Braux, Julien; Amedee, Joëlle; Laquerriere, Patrice

    2013-02-01

    Bone is a metabolically active and highly organized tissue consisting of a mineral phase of hydroxyapatite (HA) and amorphous calcium phosphate (CaP) crystals deposited in an organic matrix. One objective of bone tissue engineering is to mimic the chemical and structural properties of this complex tissue. CaP ceramics, such as sintered HA and beta-tricalcium phosphate, are widely used as bone substitutes or prosthesis coatings because of their osteoconductive properties. These ceramic interactions with tissues induce a cell response that can be different according to the composition of the material. In this review, we discuss inflammatory cell responses to CaP materials to provide a comprehensive overview of mechanisms governing the integration or loosening of implants, which remains a major concern in tissue engineering. A focus on the effects of the functionalization of CaP biomaterials highlights potential ways to increase tissue integration and limit rejection processes. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  5. The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease.

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    Jan S Suchodolski

    Full Text Available BACKGROUND: Recent molecular studies have revealed a highly complex bacterial assembly in the canine intestinal tract. There is mounting evidence that microbes play an important role in the pathogenesis of acute and chronic enteropathies of dogs, including idiopathic inflammatory bowel disease (IBD. The aim of this study was to characterize the bacterial microbiota in dogs with various gastrointestinal disorders. METHODOLOGY/PRINCIPAL FINDINGS: Fecal samples from healthy dogs (n = 32, dogs with acute non-hemorrhagic diarrhea (NHD; n = 12, dogs with acute hemorrhagic diarrhea (AHD; n = 13, and dogs with active (n = 9 and therapeutically controlled idiopathic IBD (n = 10 were analyzed by 454-pyrosequencing of the 16S rRNA gene and qPCR assays. Dogs with acute diarrhea, especially those with AHD, had the most profound alterations in their microbiome, as significant separations were observed on PCoA plots of unweighted Unifrac distances. Dogs with AHD had significant decreases in Blautia, Ruminococcaceae including Faecalibacterium, and Turicibacter spp., and significant increases in genus Sutterella and Clostridium perfringens when compared to healthy dogs. No significant separation on PCoA plots was observed for the dogs with IBD. Faecalibacterium spp. and Fusobacteria were, however, decreased in the dogs with clinically active IBD, but increased during time periods of clinically insignificant IBD, as defined by a clinical IBD activity index (CIBDAI. CONCLUSIONS: Results of this study revealed a bacterial dysbiosis in fecal samples of dogs with various GI disorders. The observed changes in the microbiome differed between acute and chronic disease states. The bacterial groups that were commonly decreased during diarrhea are considered to be important short-chain fatty acid producers and may be important for canine intestinal health. Future studies should correlate these observed phylogenetic differences with functional changes in the intestinal

  6. Acute hormonal responses in elite junior weightlifters.

    Science.gov (United States)

    Kraemer, W J; Fry, A C; Warren, B J; Stone, M H; Fleck, S J; Kearney, J T; Conroy, B P; Maresh, C M; Weseman, C A; Triplett, N T

    1992-02-01

    To date, no published studies have demonstrated resistance exercise-induced increases in serum testosterone in adolescent males. Furthermore, few data are available on the effects of training experience and lifting performance on acute hormonal responses to weightlifting in young males. Twenty-eight junior elite male Olympic-style weightlifters (17.3 +/- 1.4 yrs) volunteered for the study. An acute weightlifting exercise protocol using moderate to high intensity loads and low volume, characteristic of many weightlifting training sessions, was examined. The exercise protocol was directed toward the training associated with the snatch lift weightlifting exercise. Blood samples were obtained from a superficial arm vein at 7 a.m. (for baseline measurements), and again at pre-exercise, 5 min post-, and 15 min post-exercise time points for determination of serum testosterone, cortisol, growth hormone, plasma beta-endorphin, and whole blood lactate. The exercise protocol elicited significant (p less than or equal to 0.05) increases in each of the hormones and whole blood lactate compared to pre-exercise measures. While not being significantly older, subsequent analysis revealed that subjects with greater than 2 years training experience exhibited significant exercise-induced increases in serum testosterone from pre-exercise to 5 min post-exercise (16.2 +/- 6.2 to 21.4 +/- 7.9 nmol.l-1), while those with less than or equal to 2 years training showed no significant serum testosterone differences. None of the other hormones or whole blood lactate appear to be influenced by training experience.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Diminazene aceturate (Berenil modulates the host cellular and inflammatory responses to Trypanosoma congolense infection.

    Directory of Open Access Journals (Sweden)

    Shiby Kuriakose

    Full Text Available BACKGROUND: Trypanosoma congolense are extracellular and intravascular blood parasites that cause debilitating acute or chronic disease in cattle and other domestic animals. Diminazene aceturate (Berenil has been widely used as a chemotherapeutic agent for trypanosomiasis in livestock since 1955. As in livestock, treatment of infected highly susceptible BALB/c mice with Berenil leads to rapid control of parasitemia and survival from an otherwise lethal infection. The molecular and biochemical mechanisms of action of Berenil are still not very well defined and its effect on the host immune system has remained relatively unstudied. Here, we investigated whether Berenil has, in addition to its trypanolytic effect, a modulatory effect on the host immune response to Trypanosoma congolense. METHODOLOGY/PRINCIPAL FINDINGS: BALB/c and C57BL/6 mice were infected intraperitoneally with T. congolense, treated with Berenil and the expression of CD25 and FoxP3 on splenic cells was assessed directly ex vivo. In addition, serum levels and spontaneous and LPS-induced production of pro-inflammatory cytokines by splenic and hepatic CD11b⁺ cells were determined by ELISA. Berenil treatment significantly reduced the percentages of CD25⁺ cells, a concomitant reduction in the percentage of regulatory (CD4⁺Foxp3⁺ T cells and a striking reduction in serum levels of disease exacerbating pro-inflammatory cytokines including IL-6, IL-12, TNF and IFN-γ. Furthermore, Berenil treatment significantly suppressed spontaneous and LPS-induced production of inflammatory cytokines by splenic and liver macrophages and significantly ameliorated LPS-induced septic shock and the associated cytokine storm. CONCLUSIONS/SIGNIFICANCE: Collectively, these results provide evidence that in addition to its direct trypanolytic effect, Berenil also modulates the host immune response to the parasite in a manner that dampen excessive immune activation and production of pathology

  8. The Immune Response to Acute Focal Cerebral Ischemia and Associated Post-stroke Immunodepression: A Focused Review.

    Science.gov (United States)

    Famakin, Bolanle M

    2014-10-01

    It is currently well established that the immune system is activated in response to transient or focal cerebral ischemia. This acute immune activation occurs in response to damage, and injury, to components of the neurovascular unit and is mediated by the innate and adaptive arms of the immune response. The initial immune activation is rapid, occurs via the innate immune response and leads to inflammation. The inflammatory mediators produced during the innate immune response in turn lead to recruitment of inflammatory cells and the production of more inflammatory mediators that result in activation of the adaptive immune response. Under ideal conditions, this inflammation gives way to tissue repair and attempts at regeneration. However, for reasons that are just being understood, immunosuppression occurs following acute stroke leading to post-stroke immunodepression. This review focuses on the current state of knowledge regarding innate and adaptive immune activation in response to focal cerebral ischemia as well as the immunodepression that can occur following stroke. A better understanding of the intricate and complex events that take place following immune response activation, to acute cerebral ischemia, is imperative for the development of effective novel immunomodulatory therapies for the treatment of acute stroke.

  9. Correlation of EPO resistance with oxidative stress response and inflammatory response in patients with maintenance hemodialysis

    Directory of Open Access Journals (Sweden)

    Xiao-Hui Yan

    2017-08-01

    Full Text Available Objective: To study the correlation of erythropoietin (EPO resistance with oxidative stress response and inflammatory response in patients with maintenance hemodialysis. Methods: A total of 184 patients with end-stage renal disease who received maintenance hemodialysis in Shaanxi Provincial People’s Hospital between March 2015 and October 2016 were selected as dialysis group, 102 volunteers who received physical examination in Shaanxi Provincial People’s Hospital during the same period were selected as control group, the EPO resistance index was assessed, the median was calculated, and serum oxidative stress and inflammatory response indexes were detected. Results: Serum T-AOC, SOD and CAT levels in dialysis group were significantly lower than those in control group while MDA, AOPP, IFN-γ, HMGB-1, ICAM-1, IL-4 and IL-10 levels were significantly higher than those in control group; serum T-AOC, SOD and CAT levels in patients with high ERI were significantly lower than those in patients with low ERI while MDA, AOPP, IFN-γ, HMGB-1, ICAM-1, IL-4 and IL-10 levels were significantly higher than those in patients with low ERI. Conclusion: The degree of EPO resistance in patients with maintenance hemodialysis is closely related to the activation of oxidative stress response and inflammatory response.

  10. New Perspectives on Aspirin and the Endogenous Control of Acute Inflammatory Resolution

    Directory of Open Access Journals (Sweden)

    Thea Morris

    2006-01-01

    Full Text Available Aspirin is unique among the nonsteroidal anti-inflammatory drugs in that it has both anti-inflammatory as well as cardio-protective properties. The cardio-protective properties arise form its judicious inhibition of platelet-derived thromboxane A2 over prostacyclin, while its anti-inflammatory effects of aspirin stem from its well-established inhibition of prostaglandin (PG synthesis within inflamed tissues. Thus aspirin and the other NSAIDs have popularised the notion of inhibiting PG biosynthesis as a common anti-inflammatory strategy based on the erroneous premise that all eicosanoids are generally detrimental to inflammation. However, our fascination with aspirin has shown a more affable side to lipid mediators based on our increasing interest in the endogenous control of acute inflammation and in factors that mediate its resolution. Epi-lipoxins (epi-LXs, for instance, are produced from aspirin’s acetylation of inducible cyclooxygenase 2 (COX-2 and together with Resolvins represent an increasingly important family of immuno-regulatory and potentially cardio-protective lipid mediators. Aspirin is beginning to teach us what nature knew all along – that not all lipid mediators are bad. It seems that while some eicosanoids are pathogenic in a variety of diseases, others are unarguable protective. In this review we will re-count aspirin’s colorful history, discuss its traditional mode of action and the controversies associated therewith, as well as highlight some of the new pathways in inflammation and the cardiovascular systems that aspirin has recently revealed.

  11. DOI: 10.4025/actascibiolsci.v33i3.8011 Acta Scientiarum. Biological Sciences Maringá, v. 33, n. 3, p. 239-246, 2011 Acute inflammatory response in Nile tilapia fed probiotic Lactobacillus plantarum in the diet = Resposta inflamatória aguda em tilápia do Nilo alimentada com probiótico, Lactobacillus plantarum na dieta

    Directory of Open Access Journals (Sweden)

    Geovana Dotta

    2011-07-01

    Full Text Available The present study evaluated the acute inflammatory response induced bycarrageenin (500 £gg injected in the swim bladder of Nile tilapia, after fed or not probiotic supplemented diet. Fifty four fish were distributed in six treatments and three replicates: Group A: Fish fed unsupplemented diet: 0.5 mL saline-injected fish; fish injected with 500 £gg carrageenin diluted in 0.5 mL saline; Non-injected. Group B: Fish fed probiotic supplemented diet: saline-injected fish; carrageenin-injected fish; Non-injected. Fifteen days after feeding the fish were injected with carrageenin or saline. After six hours, inflammatory exudate was collected, as well as the blood for hematocrit, red blood cell (RBC and white blood cell (WBC counts, differential count of leucocytes and phagocytic activity in the blood. Supplementation with probiotic did not influence the RBC, hematocrit and the numbers of lymphocytes and basophils in the blood. The number of neutrophils was significantly higher in supplemented fish injected with carrageenin. Glucose concentration in supplemented and non-injected fish was higher than that observed in the saline injected ones. Probiotic potentialized the migration of cells to the inflammatory focus in the animals injected with the carrageenin irritant. In fish injected with saline and carrageenin occurred the greatest phagocytic activity in the blood in relation to those treatments.Este trabalho avaliou a resposta inflamatoria aguda induzida por injecao de carragenina (500 ƒÝg na bexiga natatoria de tilapia do Nilo suplementada ou nao com probiotico na racao. Cinquenta e quatro animais foram distribuidos em seis tratamentos com tres repeticoes: Grupo A: peixes alimentados com racao naosuplementada: Controle (injecao de 0,5 mL de solucao salina esteril; Carragenina (injecao de500 £gg de carragenina; Nao-injetada. Grupo B: peixes alimentados com racao suplementada com probiotico: Controle; Carragenina; Nao-injetada. Apos 15 dias de

  12. Acute and late radiotherapy toxicity in patients with inflammatory bowel disease

    International Nuclear Information System (INIS)

    Song, Danny Y.; Lawrie, W. Thomas; Abrams, Ross A.; Kafonek, David R.; Bayless, Theodore M.; Welsh, James S.; DeWeese, Theodore L.

    2001-01-01

    Purpose: To evaluate the incidence of gastrointestinal complications in patients with inflammatory bowel disease (IBD) receiving radiotherapy (RT) and to identify possibly avoidable factors associated with these complications. Methods and Materials: Twenty-four patients were identified and their records reviewed; all had a history of IBD before receiving RT to fields encompassing some portion of the gastrointestinal tract (Crohn's disease) or to the abdomen or pelvis (ulcerative colitis or IBD not otherwise specified). Results: Five of 24 patients (21%) experienced Grade ≥3 acute gastrointestinal toxicity; all 5 received concurrent chemotherapy. Two of 24 patients (8%) experienced Grade ≥3 late gastrointestinal toxicity. There were no significant correlations between complications and IBD type, prior IBD-related surgery, use of medications for IBD, or status of IBD. Conclusion: Patients with IBD may have an increased risk for severe acute RT-related gastrointestinal complications that is more modest than generally perceived, because all patients who had Grade ≥3 acute complications in this study had received concurrent chemotherapy (p=0.04). Further study is needed to assess this risk, as well as the impact of RT on these patients' future gastrointestinal morbidity

  13. Assessment of anti-inflammatory potential of Sesbania bispinosa Linn. leaf extracts and fractions by acute and chronic models

    OpenAIRE

    Boddawar, Ganesh D.; Dhawale, Shashikant C.; Shaikh, Shafik S.

    2016-01-01

    Aim and objectives: Leaf extracts and fractions of S. bispinosa were evaluated for anti-inflammatory activity in mice using acute and chronic anti-inflammatory models with aspirin as a reference drug. Materials and methods: Methanol, chloroform and hexane were used to prepare leaf extracts by soxhlet extraction method, while acetone, ethyl acetate and petroleum ether were used to prepare fractions of most active extract. These extract and fractions were evaluated by using carrageenan and f...

  14. DC-SIGN reacts with TLR-4 and regulates inflammatory cytokine expression via NF-κB activation in renal tubular epithelial cells during acute renal injury.

    Science.gov (United States)

    Feng, D; Wang, Y; Liu, Y; Wu, L; Li, X; Chen, Y; Chen, Y; Chen, Y; Xu, C; Yang, K; Zhou, T

    2018-01-01

    In the pathological process of acute kidney injury (AKI), innate immune receptors are essential in inflammatory response modulation; however, the precise molecular mechanisms are still unclear. Our study sought to demonstrate the inflammatory response mechanisms in renal tubular epithelial cells via Toll-like receptor-4 (TLR-4) and dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin 1 (DC-SIGN) signalling. We found that DC-SIGN exhibited strong expression in renal tubular epithelial cells of human acute renal injury tissues. DC-SIGN protein expression was increased significantly when renal tubular epithelial cells were exposed to lipopolysaccharide (LPS) for a short period. Furthermore, DC-SIGN was involved in the activation of p65 by TLR-4, which excluded p38 and c-Jun N-terminal kinases (JNK). Interleukin (IL)-6 and tumour necrosis factor (TNF)-α expression was decreased after DC-SIGN knock-down, and LPS induced endogenous interactions and plasma membrane co-expression between TLR-4 and DC-SIGN. These results show that DC-SIGN and TLR-4 interactions regulate inflammatory responses in renal tubular epithelial cells and participate in AKI pathogenesis. © 2017 British Society for Immunology.

  15. Altered inflammatory responsiveness in serotonin transporter mutant rats

    NARCIS (Netherlands)

    Macchi, F.; Homberg, J.R.; Calabrese, F.; Zecchillo, C.; Racagni, G.; Riva, M.A.; Molteni, R.

    2013-01-01

    BACKGROUND: Growing evidence suggests that alterations of the inflammatory/immune system contribute to the pathogenesis of depression. Indeed, depressed patients exhibit increased levels of inflammatory markers in both the periphery and the brain, and high comorbidity exists between major depression

  16. The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients.

    Science.gov (United States)

    Ward, Nicholas S; Casserly, Brian; Ayala, Alfred

    2008-12-01

    Like the systemic inflammatory response syndrome (SIRS), the compensatory anti-inflammatory response syndrome (CARS) is a complex pattern of immunologic responses to severe infection or injury. The difference is that while SIRS is a proinflammatory response tasked with killing infectious organisms through activation of the immune system, CARS is a global deactivation of the immune system tasked with restoring homeostasis. Much research now suggests that the timing and relative magnitude of this response have a profound impact on patient outcomes.

  17. Acute inflammatory bowel disease of the small intestine in adult: MDCT findings and criteria for differential diagnosis

    International Nuclear Information System (INIS)

    Romano, Stefania; Russo, Anna; Daniele, Stefania; Tortora, Giovanni; Maisto, Francesco; Romano, Luigia

    2009-01-01

    Inflammatory changes of the intestine leading to acute abdomen could represent a frequent diagnostic challenge for radiologists actively involved in the emergency area. MDCT imaging findings needs to be evaluated considering the clinical history and symptoms and other abdominal findings that could be of help in differential diagnosis. Several protocols have been suggested and indicated in the imaging of patient with acute intestine. However, a CT protocol in which the precontrast scanning of the abdomen is followed by i.v. administration of contrast medium using the 45-55 s delay could be effective for an optimal visualization of the bowel wall. It is important to learn to recognize how the intestine reacts to the injury and how it 'talks', in order to become aware of the different patterns of disease manifestation related to an acute intestinal condition, for an effective diagnosis of active and acute inflammatory bowel disease.

  18. Acute inflammatory bowel disease of the small intestine in adult: MDCT findings and criteria for differential diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Romano, Stefania [Department of Diagnostic Imaging, A.Cardarelli Hospital, Naples (Italy)], E-mail: stefromano@libero.it; Russo, Anna [Institute of Radiology, Second University of Naples, Naples (Italy); Daniele, Stefania; Tortora, Giovanni [Department of Diagnostic Imaging, A.Cardarelli Hospital, Naples (Italy); Maisto, Francesco [Institute of Radiology, Second University of Naples, Naples (Italy); Romano, Luigia

    2009-03-15

    Inflammatory changes of the intestine leading to acute abdomen could represent a frequent diagnostic challenge for radiologists actively involved in the emergency area. MDCT imaging findings needs to be evaluated considering the clinical history and symptoms and other abdominal findings that could be of help in differential diagnosis. Several protocols have been suggested and indicated in the imaging of patient with acute intestine. However, a CT protocol in which the precontrast scanning of the abdomen is followed by i.v. administration of contrast medium using the 45-55 s delay could be effective for an optimal visualization of the bowel wall. It is important to learn to recognize how the intestine reacts to the injury and how it 'talks', in order to become aware of the different patterns of disease manifestation related to an acute intestinal condition, for an effective diagnosis of active and acute inflammatory bowel disease.

  19. Tourniquet-induced systemic inflammatory response in extremity surgery.

    LENUS (Irish Health Repository)

    Wakai, A

    2012-02-03

    BACKGROUND: Tourniquet-induced reperfusion injury in animals produces significant systemic inflammatory effects. This study investigated whether a biologic response occurs in a clinically relevant model of tourniquet-induced reperfusion injury. METHODS: Patients undergoing elective knee arthroscopy were prospectively randomized into controls (no tourniquet) and subjects (tourniquet-controlled). The effects of tourniquet-induced reperfusion on monocyte activation state, neutrophil activation state, and transendothelial migration (TEM) were studied. Changes in the cytokines implicated in reperfusion injury, tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-10 were also determined. RESULTS: After 15 minutes of reperfusion, neutrophil and monocyte activation were significantly increased. Pretreatment of neutrophils with pooled subject (ischemia-primed) plasma significantly increased TEM. In contrast, TEM was not significantly altered by ischemia-primed plasma pretreatment of the endothelial monolayer. Significant elevation of tumor necrosis factor-alpha and IL-1beta were observed in subjects compared with controls after 15 minutes of reperfusion. There was no significant difference in serum IL-10 levels between the groups at all the time points studied. CONCLUSION: These results indicate a transient neutrophil and monocyte activation after tourniquet-ischemia that translates into enhanced neutrophil transendothelial migration with potential for tissue injury.

  20. Anti-inflammatory effect of Taraxacum officinale leaves on lipopolysaccharide-induced inflammatory responses in RAW 264.7 cells.

    Science.gov (United States)

    Koh, Yoon-Jeoung; Cha, Dong-Soo; Ko, Je-Sang; Park, Hyun-Jin; Choi, Hee-Don

    2010-08-01

    To investigate the efficacy and the mechanism of the anti-inflammatory effect of Taraxacum officinale leaves (TOLs), the effect of a methanol extract and its fractions recovered from TOLs on lipopolysaccharide (LPS)-induced responses was studied in the mouse macrophage cell line, RAW 264.7. Cells were pretreated with various concentrations of the methanol extract and its fractions and subsequently incubated with LPS (1 microg/mL). The levels of nitric oxide (NO), prostaglandin (PG) E(2), and pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were determined using enzyme-linked immunosorbent assays. Expressions of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 and activation of mitogen-activated protein (MAP) kinases were analyzed using western blotting. The methanol extract and its fractions inhibited LPS-induced production of NO, pro-inflammatory cytokines, and PGE(2) in a dose-dependent manner. The chloroform fraction significantly suppressed production of NO, PGE(2), and two pro-inflammatory cytokines (TNF-alpha and IL-1beta) in a dose-dependent manner with 50% inhibitory concentration values of 66.51, 90.96, 114.76, and 171.06 microg/mL, respectively. The ethyl acetate fraction also inhibited production of the inflammatory molecules. The chloroform and ethyl acetate fractions reduced LPS-induced expressions of iNOS and COX-2 and activation of MAP kinases in a dose-dependent manner. Among the fractions of the methanol extract, the chloroform and ethyl acetate fractions exhibited the most effective anti-inflammatory activities. These results show that the anti-inflammatory effects of TOLs are probably due to down-regulation of NO, PGE(2), and pro-inflammatory cytokines and reduced expressions of iNOS and COX-2 via inactivation of the MAP kinase signal pathway.

  1. Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

    Science.gov (United States)

    Markworth, James F.; Vella, Luke; Lingard, Benjamin S.; Tull, Dedreia L.; Rupasinghe, Thusitha W.; Sinclair, Andrew J.; Maddipati, Krishna Rao

    2013-01-01

    Classical proinflammatory eicosanoids, and more recently discovered lipid mediators with anti-inflammatory and proresolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. Using a targeted lipidomics approach, we investigated circulating lipid mediator responses to resistance exercise and treatment with the NSAID ibuprofen. Human subjects undertook a single bout of unaccustomed resistance exercise (80% of one repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo control. Venous blood was collected during early recovery (0–3 h and 24 h postexercise), and serum lipid mediator composition was analyzed by LC-MS-based targeted lipidomics. Postexercise recovery was characterized by elevated levels of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2α, and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid mediators with anti-inflammatory and proresolving properties, including arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX-2-derived prostanoids but also resulted in off-target reductions in leukotriene biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving ibuprofen. These findings characterize the blood inflammatory lipid mediator response to unaccustomed resistance exercise in humans and show that acute proinflammatory signals are mechanistically linked to the induction of a

  2. [Significance of acute-phase inflammatory reactants as an indicator of prognosis after acute myocardial infarction: which is the most useful predictor?].

    Science.gov (United States)

    Katayama, Toshiro; Nakashima, Hiroshi; Yonekura, Tsuyoshi; Honda, Yukiharu; Suzuki, Shin; Yano, Katsusuke

    2003-08-01

    To investigate the relationship between representative acute-phase inflammatory reactants [highly sensitive C-reactive protein (hsCRP), serum amyloid A protein (SAA) and interleukin-6 (IL-6)] and the severity of acute myocardial infarction and patient prognosis, and to identify the most useful predictor of the three. This study investigated 132 consecutive patients admitted within 8 hr of onset of first acute myocardial infarction and successfully reperfused with primary percutaneous coronary intervention. Acute-phase (= 24 hr from onset) blood samples were taken for evaluation of inflammatory reactants (hsCRP, SAA and IL-6), and peak creatine phosphokinase levels were measured every 4 hr after admission for 48 hr to assess myocardial infarction infarct size. Left ventriculography was performed in the chronic stage (20 +/- 9 days post-admission) to analyze left ventricular ejection fraction and regional wall motion, using Killip's classification to determine acute myocardial infarction severity. Logistic regression analysis was used to quantify the usefulness of the reactants as predictors of patient prognosis. Both hsCRP and SAA showed significant positive correlations with peak creatine phosphokinase. hsCRP and SAA showed significant inverse correlations with left ventricular ejection fraction and regional wall motion in the chronic stage. Multivariate analysis identified SAA as the best predictor of severe heart failure (Killip's classification III, IV). SAA was the best predictor of a major cardiac event (shock, cardiac death). These results suggest a strong correlation between acute-phase SAA and the clinical course of patient outcomes after acute myocardial infarction, such as cardiac function, heart failure and cardiac death. SAA may be the most useful acute-phase inflammatory reactant for predicting the prognosis after acute myocardial infarction.

  3. Endocannabinoids and inflammatory response in periodontal ligament cells.

    Science.gov (United States)

    Özdemir, Burcu; Shi, Bin; Bantleon, Hans Peter; Moritz, Andreas; Rausch-Fan, Xiaohui; Andrukhov, Oleh

    2014-01-01

    Endocannabinoids are associated with multiple regulatory functions in several tissues. The main endocannabinoids, anandamide (AEA) and 2-arachidonylglycerol (2-AG), have been detected in the gingival crevicular fluid of periodontitis patients, but the association between periodontal disease or human periodontal ligament cells (hPdLCs) and endocannabinoids still remain unclear. The aim of the present study was to examine the effects of AEA and 2-AG on the proliferation/viability and cytokine/chemokine production of hPdLCs in the presence/absence of Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS). The proliferation/viability of hPdLCs was measured using 3,4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT)-assay. Interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) levels were examined at gene expression and protein level by real-time PCR and ELISA, respectively. AEA and 2-AG did not reveal any significant effects on proliferation/viability of hPdLCs in the absence of P. gingivalis LPS. However, hPdLCs viability was significantly increased by 10-20 µM AEA in the presence of P. gingivalis LPS (1 µg/ml). In the absence of P. gingivalis LPS, AEA and 2-AG did not exhibit any significant effect on the expression of IL-8 and MCP-1 expression in hPdLCs, whereas IL-6 expression was slightly enhanced by 10 µM 2-AG and not affected by AEA. In P.gingivalis LPS stimulated hPdLCs, 10 µM AEA down-regulated gene-expression and protein production of IL-6, IL-8, and MCP-1. In contrast, 10 µM 2-AG had an opposite effect and induced a significant up-regulation of gene and protein expression of IL-6 and IL-8 (P<0.05) as well as gene-expression of MCP-1 in P. gingivalis LPS stimulated hPdLCs. Our data suggest that AEA appears to have an anti-inflammatory and immune suppressive effect on hPdLCs' host response to P.gingivalis LPS, whereas 2-AG appears to promote detrimental inflammatory processes. In conclusion, AEA and 2

  4. Endocannabinoids and inflammatory response in periodontal ligament cells.

    Directory of Open Access Journals (Sweden)

    Burcu Özdemir

    Full Text Available Endocannabinoids are associated with multiple regulatory functions in several tissues. The main endocannabinoids, anandamide (AEA and 2-arachidonylglycerol (2-AG, have been detected in the gingival crevicular fluid of periodontitis patients, but the association between periodontal disease or human periodontal ligament cells (hPdLCs and endocannabinoids still remain unclear. The aim of the present study was to examine the effects of AEA and 2-AG on the proliferation/viability and cytokine/chemokine production of hPdLCs in the presence/absence of Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS. The proliferation/viability of hPdLCs was measured using 3,4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT-assay. Interleukin-6 (IL-6, interleukin-8 (IL-8, and monocyte chemotactic protein-1 (MCP-1 levels were examined at gene expression and protein level by real-time PCR and ELISA, respectively. AEA and 2-AG did not reveal any significant effects on proliferation/viability of hPdLCs in the absence of P. gingivalis LPS. However, hPdLCs viability was significantly increased by 10-20 µM AEA in the presence of P. gingivalis LPS (1 µg/ml. In the absence of P. gingivalis LPS, AEA and 2-AG did not exhibit any significant effect on the expression of IL-8 and MCP-1 expression in hPdLCs, whereas IL-6 expression was slightly enhanced by 10 µM 2-AG and not affected by AEA. In P.gingivalis LPS stimulated hPdLCs, 10 µM AEA down-regulated gene-expression and protein production of IL-6, IL-8, and MCP-1. In contrast, 10 µM 2-AG had an opposite effect and induced a significant up-regulation of gene and protein expression of IL-6 and IL-8 (P<0.05 as well as gene-expression of MCP-1 in P. gingivalis LPS stimulated hPdLCs. Our data suggest that AEA appears to have an anti-inflammatory and immune suppressive effect on hPdLCs' host response to P.gingivalis LPS, whereas 2-AG appears to promote detrimental inflammatory processes. In conclusion

  5. Effects of urinary protease inhibitor on inflammatory response during on-pump coronary revascularisation. Effect of ulinastatin on inflammatory response.

    Science.gov (United States)

    Bingyang, J; Jinping, L; Mingzheng, L; Guyan, W; Zhengyi, F

    2007-08-01

    Cardiac surgery in patients undergoing cardiopulmonary bypass (CPB) provokes a vigorous inflammatory response with substantial clinical implications. Once the inflammatory response is triggered by CPB, leukocytes and platelets are activated by multiple stimuli. The administration of a urinary trypsin inhibitor (ulinastatin) during CPB is hypothesized to reduce cytokine release and platelet activation and to decrease pulmonary injury. We performed a prospective randomized study to investigate the influence of high-dose ulinastatin on cytokines and platelet activation and on respiratory function during and after CPB. In this pilot, prospective, randomized and double-blinded study, 30 first-time three-vessel coronary artery disease (CAD) patients undergoing coronary artery bypass graft (CABG) were randomly divided into 2 groups: U group (n=15) received a total dose of 1000000 U ulinastatin and C group (n=15) received placebo. Blood samples were withdrawn from the central vein to measure polymorphonuclear neutrophil elastase (PMNE), tumour necrosis factor-alpha (TNF-a), interleukin-6 (IL-6) and interleukin-8 (IL-8), before induction, 30 min following clamping (T2), reperfusion 3 h (T3), reperfusion 6 h (T4) and reperfusion 12 h (T5). Whole blood samples were taken for CD62P immediately before induction (as baseline), at the end of CPB (before protamine administration), 1 h after heparin neutralization by protamine and 24 h after the operation. In addition, alveolo-arterial oxygen difference (A-aDO(2)) in pulmonary gas exchange function was calculated by obtaining arterial blood gas samples before and after CPB. There were no differences in preoperative parameters between the groups. After CPB, the levels of PMNE, TNF-alfa, IL-6 and IL-8 increased in both groups over baseline values (P<0.01). The levels of PMNE, TNF-alfa, IL-6 and IL-8 in U group were significantly lower than those in C group (P<0.05). No significant differences in CD62p expression between the 2 groups

  6. The effect of dietary fatty acids on post-operative inflammatory response in a porcine model

    DEFF Research Database (Denmark)

    Langerhuus, Sine Nygaard; Jensen, Karin Hjelholt; Tønnesen, Else Kirstine

    2012-01-01

    ), sunflower oil (SO, n 28), or animal fat (AF, n 28) was evaluated with respect to post-operative responses in inflammatory markers in a porcine model on aortic vascular prosthetic graft infection. In the early post-operative period (0 ...-operative response in a number of inflammatory markers was affected by FO, and this was most apparent compared with SO....

  7. Adaptations in responsiveness of brainstem pain-modulating neurons in acute compared to chronic inflammation

    Science.gov (United States)

    Cleary, Daniel R.; Heinricher, Mary M.

    2013-01-01

    Despite similar behavioral hypersensitivity, acute and chronic pain have distinct neural bases. Here we used intraplantar injection of Complete Freund’s Adjuvant (CFA) to directly compare activity of pain-modulating neurons in the rostral ventromedial medulla (RVM) in acute versus chronic inflammation. Heat- and von Frey-evoked withdrawal reflexes and corresponding RVM neuronal activity were recorded in lightly anesthetized animals either during the first hour after CFA injection (acute) or 3–10 days later (chronic). Thermal and modest mechanical hyperalgesia during acute inflammation were associated with increases in the spontaneous activity of pain-facilitating ON-cells and suppression of pain-inhibiting OFF-cells. Acute hyperalgesia was reversed by RVM block, showing that the increased activity of RVM ON-cells is necessary for acute behavioral hypersensitivity. In chronic inflammation, thermal hyperalgesia had resolved, but mechanical hyperalgesia had become pronounced. The spontaneous discharges of ON- and OFF-cells were not different from controls, but the mechanical response thresholds for both cell classes were reduced into the innocuous range. RVM block in the chronic condition worsened mechanical hyperalgesia. These studies identify distinct contributions of RVM ON- and OFF-cells to acute and chronic inflammatory hyperalgesia. During early immune-mediated inflammation, ON-cell spontaneous activity promotes hyperalgesia. After inflammation is established, the anti-nociceptive influence of OFF-cells is dominant, yet the lowered threshold for the OFF-cell pause allows behavioral responses to stimuli that would normally be considered innocuous. The efficacy of OFF-cells in counteracting sensitization of ascending transmission pathways could therefore be an important determining factor in development of chronic inflammatory pain. PMID:23588008

  8. Adaptations in responsiveness of brainstem pain-modulating neurons in acute compared with chronic inflammation.

    Science.gov (United States)

    Cleary, Daniel R; Heinricher, Mary M

    2013-06-01

    Despite similar behavioral hypersensitivity, acute and chronic pain have distinct neural bases. We used intraplantar injection of complete Freund's adjuvant to directly compare activity of pain-modulating neurons in the rostral ventromedial medulla (RVM) in acute vs chronic inflammation. Heat-evoked and von Frey-evoked withdrawal reflexes and corresponding RVM neuronal activity were recorded in lightly anesthetized animals either during the first hour after complete Freund's adjuvant injection (acute) or 3 to 10 days later (chronic). Thermal and modest mechanical hyperalgesia during acute inflammation were associated with increases in the spontaneous activity of pain-facilitating ON-cells and suppression of pain-inhibiting OFF-cells. Acute hyperalgesia was reversed by RVM block, showing that the increased activity of RVM ON-cells is necessary for acute behavioral hypersensitivity. In chronic inflammation, thermal hyperalgesia had resolved but mechanical hyperalgesia had become pronounced. The spontaneous discharges of ON- and OFF-cells were not different from those in control subjects, but the mechanical response thresholds for both cell classes were reduced into the innocuous range. RVM block in the chronic condition worsened mechanical hyperalgesia. These studies identify distinct contributions of RVM ON- and OFF-cells to acute and chronic inflammatory hyperalgesia. During early immune-mediated inflammation, ON-cell spontaneous activity promotes hyperalgesia. After inflammation is established, the antinociceptive influence of OFF-cells is dominant, yet the lowered threshold for the OFF-cell pause allows behavioral responses to stimuli that would normally be considered innocuous. The efficacy of OFF-cells in counteracting sensitization of ascending transmission pathways could therefore be an important determining factor in development of chronic inflammatory pain. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All

  9. Effects of asphalt fume condensate exposure on acute pulmonary responses

    Energy Technology Data Exchange (ETDEWEB)

    Ma, J.Y.C.; Barger, M.W.; Castranova, V. [Health Effects Lab. Div., National Inst. for Occupational Safety and Health, Morgantown, WV (United States); Kriech, A.J. [Heritage Research Group, Indianapolis, IN (United States)

    2000-10-01

    The present study was carried out to characterize the effects of in vitro exposure to paving asphalt fume condensate (AFC) on alveolar macrophage (AM) functions and to monitor acute pulmonary responses to in vivo AFC exposure in rats. Methods: For in vitro studies, rat primary AM cultures were incubated with various concentrations of AFC for 24 h at 37 C. AM-conditioned medium was collected and assayed for lactate dehydrogenase (LDH) as a marker of cytotoxicity. Tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-1 (IL-1) production were assayed in AM-conditioned medium to monitor AM function. The effect of AFC on chemiluminescence (CL) generated by resting AM or AM in response to zymosan or PMA stimulation was also determined as a marker of AM activity. For in vivo studies, rats received either (1) a single intratracheal (IT) instillation of saline, or 0.1 mg or 0.5 mg AFC and were killed 1 or 3 days later; or (2) IT instillation of saline, or 0.1, 0.5, or 2 mg AFC for three consecutive days and were killed the following day. Differential counts of cells harvested by bronchoalveolar lavage were measured to monitor inflammation. Acellular LDH and protein content in the first lavage fluid were measured to monitor damage. CL generation, TNF-{alpha} and IL-1 production by AM were assayed to monitor AM function. Results: In vitro AFC exposure at <200 {mu}g/ml did not induce cytotoxicity, oxidant generation, or IL-1 production by AM, but it did cause a small but significant increase in TNF-{alpha} release from AM. In vitro exposure of AM to AFC resulted in a significant decline of CL in response to zymosan or PMA stimulation. The in vivo studies showed that AFC exposure did not induce significant neutrophil infiltration or alter LDH or protein content in acellular lavage samples. Macrophages obtained from AFC-exposed rats did not show significant differences in oxidant production or cytokine secretion at rest or in response to LPS in comparison with control

  10. Effect of short-term weight loss on mental stress-induced cardiovascular and pro-inflammatory responses in women.

    Science.gov (United States)

    Endrighi, Romano; Hamer, Mark; Hackett, Ruth A; Carvalho, Livia A; Jackson, Sarah E; Wardle, Jane; Steptoe, Andrew

    2015-01-01

    Epidemiologic evidence links psychosocial stress with obesity but experimental studies examining the mechanisms that mediates the effect of stress on adiposity are scarce. The aim of this study was to investigate whether changes in adiposity following minimal weight loss affect heightened stress responses in women, and examine the role of the adipokine leptin in driving inflammatory responses. Twenty-three overweight or obese, but otherwise healthy, women (M age = 30.41 ± 8.0 years; BMI = 31.9 ± 4.1 kg/m(2)) completed standardized acute mental stress before and after a 9-week calorie restriction program designed to modify adiposity levels. Cardiovascular (blood pressure and heart rate) and inflammatory cytokines (leptin and interleukin-6; IL-6) responses to mental stress were assessed several times between baseline and a 45-min post-stress recovery period. There were modest changes in adiposity measures while the adipokine leptin was markedly reduced (-27%) after the intervention. Blood pressure reactivity was attenuated (-3.38 ± 1.39 mmHg) and heart rate recovery was improved (2.07 ± 0.96 Bpm) after weight loss. Blood pressure responses were inversely associated with changes in waist to hip ratio post intervention. Decreased levels of circulating leptin following weight loss were inversely associated with the IL-6 inflammatory response to stress (r = -0.47). We offered preliminary evidence suggesting that modest changes in adiposity following a brief caloric restriction program may yield beneficial effect on cardiovascular stress responses. In addition, reductions in basal leptin activity might be important in blunting pro-inflammatory responses. Large randomized trials of the effect of adiposity on autonomic responses are thus warranted.

  11. Anti-inflammatory treatment and risk of depression in 91,842 patients with acute coronary syndrome and 91,860 individuals without acute coronary syndrome in Denmark

    DEFF Research Database (Denmark)

    Wium-Andersen, Ida Kim; Wium-Andersen, Marie Kim; Jørgensen, Martin Balslev

    2017-01-01

    Background We examined if treatment with acetylsalicylic acid (ASA), non-steroid anti-inflammatory drugs (NSAID), or statins after acute coronary syndrome (ACS) are associated with decreased risk of depression. Method This register-based cohort study included all individuals with a first...

  12. Potential use of salivary markers for longitudinal monitoring of inflammatory immune responses to vaccination

    NARCIS (Netherlands)

    Lim, Pei Wen; Garssen, Johan; Sandalova, Elena

    2016-01-01

    Vaccination, designed to trigger a protective immune response against infection, is a trigger for mild inflammatory responses. Vaccination studies can address the question of inflammation initiation, levels, and resolution as well as its regulation for respective studied pathogens. Such studies

  13. Effects of blood products on inflammatory response in endothelial cells in vitro.

    Directory of Open Access Journals (Sweden)

    Martin Urner

    Full Text Available BACKGROUND: Transfusing blood products may induce inflammatory reactions within the vascular compartment potentially leading to a systemic inflammatory response. Experiments were designed to assess the inflammatory potential of different blood products in an endothelial cell-based in vitro model and to compare baseline levels of potentially activating substances in transfusion products. METHODS: The inflammatory response from pre-activated (endotoxin-stimulated and non-activated endothelial cells as well as neutrophil endothelial transmigration in response to packed red blood cells (PRBC, platelet concentrates (PC and fresh frozen plasma (FFP was determined. Baseline inflammatory mediator and lipid concentrations in blood products were evaluated. RESULTS: Following incubation with all blood products, an increased inflammatory mediator release from endothelial cells was observed. Platelet concentrates, and to a lesser extent also FFP, caused the most pronounced response, which was accentuated in already pre-stimulated endothelial cells. Inflammatory response of endothelial cells as well as blood product-induced migration of neutrophils through the endothelium was in good agreement with the lipid content of the according blood product. CONCLUSION: Within the group of different blood transfusion products both PC and FFP have a high inflammatory potential with regard to activation of endothelial cells. Inflammation upon blood product exposure is strongly accentuated when endothelial cells are pre-injured. High lipid contents in the respective blood products goes along with an accentuated inflammatory reaction from endothelial cells.

  14. Fasting levels of insulin and amylin after acute pancreatitis are associated with pro-inflammatory cytokines.

    Science.gov (United States)

    Gillies, Nicola A; Pendharkar, Sayali A; Singh, Ruma G; Windsor, John A; Bhatia, Madhav; Petrov, Maxim S

    2017-10-01

    The prevalence of metabolic diseases continues to rise worldwide, with a growing recognition of metabolic dysregulation after acute inflammatory diseases such as acute pancreatitis (AP). Adipokines and cytokines play an important role in metabolism and the course of AP, but there is a paucity of research investigating their relationship with pancreatic hormones after AP. This study aimed to explore associations between pancreatic hormones and adipokines as well as cytokines to provide insights into the pathophysiology of altered pancreatic hormone secretion following AP. A total of 83 patients previously diagnosed with AP and no prior diabetes or pre-diabetes were recruited into this cross-sectional follow up study. Fasting venous blood samples were collected to analyse a panel of pancreatic hormones and derivatives (amylin, C-peptide, glucagon, insulin, pancreatic polypeptide, somatostatin), adipokines (adiponectin, leptin, retinol binding protein-4, and resistin), and cytokines (interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumour necrosis factor-α (TNF-α)). Linear regression analyses were used, and potential confounders were adjusted for in multivariate analyses. Insulin was significantly associated with IL-6 in both unadjusted and adjusted models (p = .029 and p = .040, respectively). Amylin was significantly associated with MCP-1 in the unadjusted model (p = .046), and TNF-α in unadjusted and adjusted models (p = .025 and p = .027, respectively). Insulin and amylin have a strong positive association with pro-inflammatory cytokines in patients following an episode of AP. These associations have possible relevance in the development of diabetes associated with diseases of the exocrine pancreas, providing the opportunity to develop novel treatment paradigms.

  15. Acute stress responses in Chinese soldiers performing various military tasks

    OpenAIRE

    Huang, Peng; Zhang, Tengxiao; Miao, Danmin; Zhu, Xia

    2014-01-01

    Background To examine Chinese soldiers’ acute stress responses, we did this study. Methods The soldiers completed the Acute Stress Response Scale (ASRS) when engaged in major tasks, such as earthquake rescue in Wenchuan, Sichuan, and maintaining social stability in Urumchi, Xinjiang. The ASRS has good reliability and validity. The study enrolled 1,832 male soldiers. Results The results showed significant differences among five dimensions and the overall response index when comparing four dive...

  16. Modulation of inflammatory response arising from high-intensity intermittent and concurrent strength training in physically active males.

    Science.gov (United States)

    Monteiro, Paula Alves; Campos, Eduardo Zapaterra; de Oliveira, Flaviane Poleto; Peres, Fernando Pierin; Rosa-Neto, José Cesar; Pimentel, Gustavo Duarte; Lira, Fabio Santos

    2017-03-01

    The purposes of this study were to determine: (i) the extent of an acute session of high-intensity intermittent exercise (HIIE) followed by a concurrent strength session (Conc) on the increase of systemic inflammatory cytokines and chemokines, and (ii) whether eight weeks of high intensity interval training plus concurrent strength training alters the acute inflammatory response and immune status. Ten recreationally active males (aged 26.9±4.3years) performed two experimental exercise sessions interspersed by eight weeks of HIIT plus concurrent strength training. The experimental exercise session was composed of a 5-km run on a treadmill (1:1 at 100% of maximal aerobic speed (MAS)), and after 10min of passive recovery, back squat exercises were performed (80% 1RM, four sets until exhaustion). Serum samples were collected after fasting, pre-HIIE, post-HIIE, Pre-Conc, Post-Conc, and 30 and 60min post-exercise session. The comparison between both concurrent exercise sessions was performed using repeated measure ANOVA, with the Bonferroni Post-hoc when necessary. Interleukin-6 (IL-6) presented a moment effect (F=6.72; pconcurrent training probably occurred at Post-Conc (11.42±3.09pgmL -1 and 8.88±1.29pgmL -1 ). In addition, maintenance of immune function was observed. Therefore, HIIE and concurrent strength exercise lead to an increase in cytokines response, but eight weeks of training program promoted anti-inflammatory response after an acute session of concurrent exercise. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Modulation of inflammatory and immune responses by vitamin D.

    Science.gov (United States)

    Colotta, Francesco; Jansson, Birger; Bonelli, Fabrizio

    2017-12-01

    Vitamin D (VitD) is a prohormone most noted for the regulation of calcium and phosphate levels in circulation, and thus of bone metabolism. Inflammatory and immune cells not only convert inactive VitD metabolites into calcitriol, the active form of VitD, but also express the nuclear receptor of VitD that modulates differentiation, activation and proliferation of these cells. In vitro, calcitriol upregulates different anti-inflammatory pathways and downregulates molecules that activate immune and inflammatory cells. Administration of VitD has beneficial effects in a number of experimental models of autoimmune disease. Epidemiologic studies have indicated that VitD insufficiency is frequently associated with immune disorders and infectious diseases, exacerbated by increasing evidence of suboptimal VitD status in populations worldwide. To date, however, most interventional studies in human inflammatory and immune diseases with VitD supplementation have proven to be inconclusive. One of the reasons could be that the main VitD metabolite measured in these studies was the 25-hydroxyVitD (25OHD) rather than its active form calcitriol. Although our knowledge of calcitriol as modulator of immune and inflammatory reactions has dramatically increased in the past decades, further in vivo and clinical studies are needed to confirm the potential benefits of VitD in the control of immune and inflammatory conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Early inflammatory response in epithelial ovarian tumor cyst fluids

    International Nuclear Information System (INIS)

    Kristjánsdóttir, Björg; Partheen, Karolina; Fung, Eric T; Yip, Christine; Levan, Kristina; Sundfeldt, Karin

    2014-01-01

    Mortality rates for epithelial ovarian cancer (EOC) are high, mainly due to late-stage diagnosis. The identification of biomarkers for this cancer could contribute to earlier diagnosis and increased survival rates. Given that chronic inflammation plays a central role in cancer initiation and progression, we selected and tested 15 cancer-related cytokines and growth factors in 38 ovarian cyst fluid samples. We used ovarian cyst fluid since it is found in proximity to the pathology and mined it for inflammatory biomarkers suitable for early detection of EOC. Immunoprecipitation and high-throughput sample fractionation were obtained by using tandem antibody libraries bead and mass spectrometry. Two proteins, monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleucin-8 (IL-8/CXCL8), were significantly (P < 0.0001) higher in the malignant (n = 16) versus benign (n = 22) tumor cysts. Validation of MCP-1, IL-8, and growth-regulated protein-α (GROα/CXCL1) was performed with ELISA in benign, borderline, and malignant cyst fluids (n = 256) and corresponding serum (n = 256). CA125 was measured in serum from all patients and used in the algorithms performed. MCP-1, IL-8, and GROα are proinflammatory cytokines and promoters of tumor growth. From 5- to 100-fold higher concentrations of MCP-1, IL-8 and GROα were detected in the cyst fluids compared to the serum. Significant (P < 0.001) cytokine response was already established in borderline cyst fluids and stage I EOC. In serum a significant (P < 0.01) increase of IL-8 and GROα was found, but not until stage I and stage III EOC, respectively. These findings confirm that early events in tumorigenesis can be analyzed and detected in the tumor environment and we conclude that ovarian cyst fluid is a promising source in the search for new biomarkers for early ovarian tumors

  19. Effect of Dietary Lipids on Endotoxemia Influences Postprandial Inflammatory Response.

    Science.gov (United States)

    López-Moreno, Javier; García-Carpintero, Sonia; Jimenez-Lucena, Rosa; Haro, Carmen; Rangel-Zúñiga, Oriol A; Blanco-Rojo, Ruth; Yubero-Serrano, Elena M; Tinahones, Francisco J; Delgado-Lista, Javier; Pérez-Martínez, Pablo; Roche, Helen M; López-Miranda, José; Camargo, Antonio

    2017-09-06

    Metabolic syndrome (MetS) results in postprandial metabolic alterations that predisposes one to a state of chronic low-grade inflammation and increased oxidative stress. We aimed to assess the effect of the consumption of the quantity and quality of dietary fat on fasting and postprandial plasma lipopolysaccharides (LPS). A subgroup of 75 subjects with metabolic syndrome was randomized to receive 1 of 4 diets: HSFA, rich in saturated fat; HMUFA, rich in monounsaturated fat; LFHCC n-3, low-fat, rich in complex carbohydrate diet supplemented with n-3 polyunsaturated fatty acids; LFHCC low-fat, rich in complex carbohydrate diet supplemented with placebo, for 12 weeks each. We administered a fat challenge reflecting the fatty acid composition of the diets at postintervention. We determined the plasma lipoproteins and glucose and gene expression in peripheral blood mononuclear cells (PBMC) and adipose tissue. LPS and LPS binding protein (LBP) plasma levels were determined by ELISA, at fasting and postprandial (4 h after a fat challenge) states. We observed a postprandial increase in LPS levels after the intake of the HSFA meal, whereas we did not find any postprandial changes after the intake of the other three diets. Moreover, we found a positive relationship between the LPS plasma levels and the gene expression of IkBa and MIF1 in PBMC. No statistically significant differences in the LBP plasma levels at fasting or postprandial states were observed. Our results suggest that the consumption of HSFA diet increases the intestinal absorption of LPS which, in turn, increases postprandial endotoxemia levels and the postprandial inflammatory response.

  20. Lactic acid delays the inflammatory response of human monocytes

    International Nuclear Information System (INIS)

    Peter, Katrin; Rehli, Michael; Singer, Katrin; Renner-Sattler, Kathrin; Kreutz, Marina

    2015-01-01

    Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. - Highlights: • Lactic acid broadly delays LPS-induced gene expression in human monocytes. • Expression of important monocyte effector molecules is affected by lactic acid. • Interference of lactic acid with TLR signaling causes the delayed gene expression. • The profound effect of lactic acid might contribute to immune suppression in tumors

  1. Diagnostic and predictive value of acute-phase reactants in adult undifferentiated peripheral inflammatory arthritis: a systematic review

    NARCIS (Netherlands)

    Vercoutere, Ward; Thevissen, Kristof; Bombardier, Claire; Landewé, Robert B. M.

    2011-01-01

    To review the available literature on the diagnostic and predictive value of acute-phase reactants in adult undifferentiated peripheral inflammatory arthritis (UPIA) as an evidence base for generating multinational clinical practice recommendations in the 3e Initiative in Rheumatology. A systematic

  2. Co-existence of acute appendicitis and inflammatory myofibroblastic tumor of the small intestine: A case report

    Directory of Open Access Journals (Sweden)

    Nurcan Unver

    2015-09-01

    Conclusion: Coexistence of inflammatory myofibroblastic tumor located in the gastrointestinal system with acute appendicitis is a rare event. Complete surgical excision should be regarded as the mainstay of the treatment. Long-term follow up with serial imaging techniques is recommended.

  3. Immune reconstitution inflammatory syndrome Kaposi sarcoma in the liver manifesting as acute obstructive hepatitis: another potential role for montelukast?

    Science.gov (United States)

    Read, P J; Lucas, S; Morris, S; Kulasegaram, R

    2013-02-01

    Immune reconstitution inflammatory syndrome has been described in Kaposi sarcoma, but does not usually manifest as acute hepatitis. We describe a case of rapid obstructive jaundice after initiation of antiretroviral therapy, in which the liver biopsy confirmed hepatic Kaposi sarcoma, and the clinical course was altered by the addition of montelukast.

  4. Acute-onset chronic inflammatory demyelinating polyneuropathy with cranial nerve involvement, dysautonomia, respiratory failure, and autoantibodies.

    Science.gov (United States)

    Hantson, Philippe; Kevers, Luc; Fabien, Nicole; Van Den Bergh, Peter

    2010-03-01

    We examined a 27-year-old woman who developed rapidly progressive quadriplegia and acute respiratory failure that required mechanical ventilation in the intensive care unit. It was unclear whether this was a presentation of Guillain-Barré syndrome (GBS) or acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP). Remarkable features included multiple cranial nerve involvement, respiratory failure, dysautonomia, and skin manifestations. Several autoantibodies were elevated, including antinuclear (ANA), anticardiolipin (aCL), thyroid, and calcium-sensing receptor (CaSR) autoantibodies. The patient was initially diagnosed with GBS and treated with intravenous immunoglobulin (IVIg). After almost complete recovery, relapse with quadriplegia and respiratory failure was observed 12 weeks after motor symptom onset. She then received IVIg and steroid pulse therapy followed by maintenance oral methylprednisolone and plasma exchange. She recovered completely 4 months after the relapse. The further clinical and serological course was consistent with systemic lupus erythematosus (SLE)-associated CIDP. Herein we evaluate the association between A-CIDP and some biological markers of autoimmunity.

  5. Does dienogest influence the inflammatory response of endometriotic cells? A systematic review.

    Science.gov (United States)

    Grandi, Giovanni; Mueller, Michael; Bersinger, Nick A; Cagnacci, Angelo; Volpe, Annibale; McKinnon, Brett

    2016-03-01

    A systematic review of all literature was done to assess the ability of the progestin dienogest (DNG) to influence the inflammatory response of endometriotic cells. In vitro and in vivo studies report an influence of DNG on the inflammatory response in eutopic or ectopic endometrial tissue (animal or human). After strict inclusion criteria were satisfied, 15 studies were identified that reported a DNG influence on the inflammatory response in endometrial tissue. These studies identified a modulation of prostaglandin (PG) production and metabolism (PGE2, PGE2 synthase, cyclo-oxygenase-2 and microsomal PGE synthase-1), pro-inflammatory cytokine and chemokine production [interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, monocyte chemoattractant protein-1 and stromal cell-derived factor-1], growth factor biosynthesis (vascular endothelial growth factor and nerve growth factor) and signaling kinases, responsible for the control of inflammation. Evidence supports a progesterone receptor-mediated inhibition of the inflammatory response in PR-expressing epithelial cells. It also indicated that DNG inhibited the inflammatory response in stromal cells, however, whether this was via a PR-mediated mechanism is not clear. DNG has a significant effect on the inflammatory microenvironment of endometriotic lesions that may contribute to its clinical efficacy. A better understanding of the specific anti-inflammatory activity of DNG and whether this contributes to its clinical efficacy can help develop treatments that focus on the inhibition of inflammation while minimizing hormonal modulation.

  6. Evaluation of inflammatory cytokines as prognostic markers in experimental acute pancreatitis in rats

    Directory of Open Access Journals (Sweden)

    Haim Paran

    2000-06-01

    Full Text Available Background: Early evaluation of the severity of acute pancreatitis requires measurements of many variables. Clinical parameters as well as CT scan have traditionally been used as predictors of severity, and complications. None of them however can predict the outcome early and reliably. Inflammatory cytokines were shown to play an important role in the inflammatory cascade, which occurs early in the course of the disease. The aim of the present study is to evaluate the predictive value of plasma interleukin-6 (IL-6 and interleukin-1 (IL-1 levels in experimental pancreatitis in rats. Methods: Male wistar rats were anesthetized and pancreatitis was induced by intraparenchymal injection of 5% (group 2 and 10% (group 3 sodium taurocholate (TC, resulting in 2 distinct groups of severity. In sham controls (group 1, saline was injected into the pancreas in the same fashion. Blood samples were obtained before and 2, 4, 24, and 96 hours after the induction of pancreatitis and plasma amylase, lipase, LDH, IL-1 and IL-6 levels were measured. Mortality was recorded every 8 hours. Pancreatitis severity was also assessed by histopathology. Results: Four hours after pancreatitis induction, plasma amylase, lipase and LDH levels were markedly increased in the pancreatitis groups. In the sham control group, moderate increases were also observed. No consistent significant difference in amylase, lipase or LDH levels was observed between the groups. At 2 hours from pancreatitis induction, IL-6 levels increased mildly in-groups 1 and 2, and decreased to the baseline levels at 24 hours. In-group 3, the increase in IL-6 levels was significantly higher then in-groups 1 and 2 (p=0.029 and 0.036 respectively, and correlated well with pancreatitis severity as defined by pathology (p=0.01 and mortality rates (p=0.037. No difference in IL-1 levels was observed at 2,4 and 24 hours from induction. At 96 hours IL-1 levels were higher in group 3 then in groups 1 and 2 (p=0

  7. Acute stress responses in Chinese soldiers performing various military tasks.

    Science.gov (United States)

    Huang, Peng; Zhang, Tengxiao; Miao, Danmin; Zhu, Xia

    2014-01-01

    To examine Chinese soldiers' acute stress responses, we did this study. The soldiers completed the Acute Stress Response Scale (ASRS) when engaged in major tasks, such as earthquake rescue in Wenchuan, Sichuan, and maintaining social stability in Urumchi, Xinjiang. The ASRS has good reliability and validity. The study enrolled 1,832 male soldiers. The results showed significant differences among five dimensions and the overall response index when comparing four diverse military tasks. Further analysis found that reduced work efficiency and 24 symptom clusters were significantly positively correlated. The acute stress response of soldiers performing various tasks was influenced by many factors, including the task characteristics and external factors. In addition, the acute stress response affected their work efficiency.

  8. Effect of PAS triple therapy on nerve injury, oxidative stress and inflammatory response in patients with cerebral infarction

    Directory of Open Access Journals (Sweden)

    Li-Jun Deng

    2017-10-01

    Full Text Available Objective: To study the effect of probucol + aspirin + atorvastatin (PAS triple therapy on nerve injury, oxidative stress and inflammatory response in patients with cerebral infarction. Methods: Patients with acute cerebral infarction who were treated in Affiliated Hospital of Jianghan University between February 2015 and January 2015 were selected and randomly divided into the PAS group who received probucol + aspirin + atorvastatin triple therapy and the control group who received aspirin + atorvastatin double therapy. The markers of nerve injury, oxidative stress and inflammatory response were determined before treatment and 15 d after treatment. Results: 15 d after treatment, peripheral blood Keap-1 expression and serum GPX1 contents of both groups of patients were significantly higher than those before treatment while peripheral blood Nrf-2 and ARE expression as well as serum S100B, NSE, sTRAIL, FKN, HMGB-1, sICAM-1, Chemerin and 8-iso-PGF2α contents were significantly lower than those before treatment, and peripheral blood Keap-1 expression and serum GPX1 content of PAS group were significantly higher than those of control group while peripheral blood Nrf-2 and ARE expression as well as serum S100B, NSE, sTRAIL, FKN, HMGB-1, sICAM-1, Chemerin and 8-iso-PGF2α contents were significantly lower than those of control group. Conclusion: PAS triple therapy can reduce the nerve injury as well as oxidative stress response and inflammatory response in patients with cerebral infarction.

  9. The inflammatory an immune response to mousepox (infectious ectromelia) virus

    International Nuclear Information System (INIS)

    Niemialtowski, M.G.; Spohr de Faundez, I.; Gierynska, M; Toka, F.N.; Schollenberger, A.; Popis, A.; Malicka, E.

    1994-01-01

    The ectromelia virus(EV) has been recognized as the etiological agent of a relatively common infection in laboratory mouse colonies around the world, i.e. Europe (including Poland), U.S.A. and Asia. Due to widespread use of mice in biomedical research, it is important to study the biology of strains characteristic for a given country. This is particularly significant for the diagnosis, prevention and control ectromelia. In severe epizootics, approximately 90% morbidity is observed within colonies and mortality rate exceeding 70% is observed within 4 to 20 days from the appearance of clinical symptoms. The resistance to lethal infection is mouse strain-dependent. Several inbred strains of mice, including C57BL/6 and AKR are resistant to the lethal effects of EV infection, while others, such as A and BALB/c are susceptible. Recent studies indicate that (1) T lymphocytes, natural killer cells and interferon (IFN)-dependent host defenses must operate for the expression of resistance, (2) virus-specific T-cell precursors appear earlier in regional lymph nodes of resistant than susceptible mice, and (3) resistance mechanism are expressed during early stages of infection. Over the past several years, (1) induction of anti-EV cytotoxic CD8 + T lymphocytes responses in vivo in the absence of CD 4 + (T helper) cells, (2) importance of some cytokines e.g., IFN-gamma in EV clearance at all stages of infection, and (3) induction of nitric oxide synthase, which is necessary for a substantial antiviral activity of IFN-gamma, have been demonstrated. The effector mechanism by which EV-specific immune cells (T lymphocytes) execute their and inflammatory functions are thought to involve the release of soluble mediators that attract, focus and active cells at the infected sites. It is possible that the skin is the most relevant organ for studying the biology of an EV infection in vivo, yet very little is known concerning EV replication there and the importance of the skin;s innate and

  10. Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats.

    Science.gov (United States)

    Morales, Glauco; Paredes, Adrián; Olivares, Alberto; Bravo, Jaime

    2014-03-26

    Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae) widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. Oral administration of hydroalcoholic extract (HAE) at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE) from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE) significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69%) was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04 ± 0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg) gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg) induced an anti-inflammatory effect greater than (or comparable) with the effect of indomethacin from 2nd to 4th hours of the experiment. Our results reveal for first time that compounds contained in the hydroalcoholic extract of Lampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti-inflammatory activity may be associated with the presence of flavonoids. These

  11. Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats

    Directory of Open Access Journals (Sweden)

    Glauco Morales

    2014-01-01

    Full Text Available BACKGROUND: Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. RESULTS: Oral administration of hydroalcoholic extract (HAE at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69% was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04±0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg induced an anti-inflammatory effect greater than (or comparable with the effect of indomethacin from 2nd to 4th hours of the experiment. CONCLUSIONS: Our results reveal for first time that compounds contained in the hydroalcoholic extract ofLampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti-inflammatory

  12. Delivery strategies to control inflammatory response: Modulating M1-M2 polarization in tissue engineering applications

    OpenAIRE

    Alvarez, Mario Moisés; Liu, Julie C.; Santiago, Grissel Trujillo-de; Cha, Byung-Hyun; Vishwakarma, Ajaykumar; Ghaemmaghami, Amir; Khademhosseini, Ali

    2016-01-01

    Macrophages are key players in many physiological scenarios including tissue homeostasis. In response to injury, typically the balance between macrophage sub-populations shifts from an M1 phenotype (pro-inflammatory) to an M2 phenotype (anti-inflammatory). In tissue engineering scenarios, after implantation of any device, it is desirable to exercise control on this M1-M2 progression and to ensure a timely and smooth transition from the inflammatory to the healing stage. In this review, we bri...

  13. Inflammatory responses after laparoscopic uterine myomectomy compared to open surgery in current clinical practice

    International Nuclear Information System (INIS)

    Holub, Z.; Kliment, L.; Jabor, A.; Sprongl, L.

    2006-01-01

    Objective was to determine the differences in inflammatory response and clinical outcome of current clinical practice in women undergoing laparoscopic myomectomy (LM) and abdominal myomectomy (AM) for symptomatic fibroid. A total of 36 women entered the study between October 2004 to June 2005 at the Department of Gynecology and Obstetrics and the Endosopy Training Center at the Baby Friendly Hospital in Klando, Czech Republic, based upon an ultrasonographic assessment size of dominant fibroid (DM) before surgery. All women were allocated to one of 2 groups: group 1 (n=17), DM -6cm, treated with open myomectomy. Surgical characteristics, hospital stay and complications were analyzed. Blood samples for assay of the acute phase reactants and markers of tissue trauma [C-reactive protein (CRP), interleukin-6 (IL-6), serum amyloid kinase (CK)] were taken preoperatively and on the first and third postoperative day. The difference between the groups in mean size of DM was statistically significant (4.8 cm in group 1 versus 6.9 cm in group 2, p<0.05). Statistically, significant differences were found between the compared groups in intra-operative blood loss (p<0.05) and length of hospital stay (p<0.001). No complication was reported after LM. There were significantly higher levels of CRP, IL-6, SAA, WBC and CK in both groups after surgery. Increased levels of IL-6, WBC and CK were greatest on the first postoperative day in the open group. The serum CRP, IL-6, SAA, WBC, CK and the fall in the hemoglobin were statistically different between the 2 groups. Compared with open myomectomy, LM was associated with a less intensive inflammatory response and a more favorable clinical outcome. (author)

  14. Pharmacological characterisation of anti-inflammatory compounds in acute and chronic mouse models of cigarette smoke-induced inflammation

    Directory of Open Access Journals (Sweden)

    Mok Joanie

    2010-09-01

    Full Text Available Abstract Background Candidate compounds being developed to treat chronic obstructive pulmonary disease are typically assessed using either acute or chronic mouse smoking models; however, in both systems compounds have almost always been administered prophylactically. Our aim was to determine whether the prophylactic effects of reference anti-inflammatory compounds in acute mouse smoking models reflected their therapeutic effects in (more clinically relevant chronic systems. Methods To do this, we started by examining the type of inflammatory cell infiltrate which occurred after acute (3 days or chronic (12 weeks cigarette smoke exposure (CSE using female, C57BL/6 mice (n = 7-10. To compare the effects of anti-inflammatory compounds in these models, mice were exposed to either 3 days of CSE concomitant with compound dosing or 14 weeks of CSE with dosing beginning after week 12. Budesonide (1 mg kg-1; i.n., q.d., roflumilast (3 mg kg-1; p.o., q.d. and fluvastatin (2 mg kg-1; p.o., b.i.d. were dosed 1 h before (and 5 h after for fluvastatin CSE. These dose levels were selected because they have previously been shown to be efficacious in mouse models of lung inflammation. Bronchoalveolar lavage fluid (BALF leukocyte number was the primary endpoint in both models as this is also a primary endpoint in early clinical studies. Results To start, we confirmed that the inflammatory phenotypes were different after acute (3 days versus chronic (12 weeks CSE. The inflammation in the acute systems was predominantly neutrophilic, while in the more chronic CSE systems BALF neutrophils (PMNs, macrophage and lymphocyte numbers were all increased (p Conclusions These results demonstrate that the acute, prophylactic systems can be used to identify compounds with therapeutic potential, but may not predict a compound's efficacy in chronic smoke exposure models.

  15. Development of a new humanized mouse model to study acute inflammatory arthritis

    Directory of Open Access Journals (Sweden)

    Misharin Alexander V

    2012-09-01

    Full Text Available Abstract Background Substantial advances have been generated in understanding the pathogenesis of rheumatoid arthritis (RA. Current murine models of RA-like disease have provided great insights into the molecular mechanism of inflammatory arthritis due to the use of genetically deficient or transgenic mice. However, these studies are limited by differences that exist between human and murine immune systems. Thus, the development of an animal model that utilizes human immune cells, will afford the opportunity to study their function in the initiation and propagation of inflammatory arthritis. Methods One to two-day old irradiated NOD-scid IL2rγnull (NSG mice were reconstituted with human CD34+ cord blood stem cells. Leukocytes were analyzed by flow cytometry and circulating antibodies were determined by ELISA. Arthritis was induced by injecting complete Freund’s adjuvant into knee or ankle joints. Mice were also treated with the TNF inhibitor, Etanercept, or PBS and joints were analyzed histologically. Results Humanized mice were established with high reconstitution rates and were able to spontaneously produce human immunoglobulins as well as specific IgG in response to immunization. Intraperitoneal injection of thioglycolate or injection of complete Freund’s adjuvant into joints resulted in migration of human immune cells to the injected sites. Arthritic humanized mice treated with Etanercept had markedly less inflammation, which was associated with decreased total numbers of human CD45+ cells, including human lymphocytes and neutrophils. Conclusions The humanized mouse model is a new model to study inflammatory arthritis disease using human leukocytes without rejection of engrafted tissue. Future studies may adapt this system to incorporate RA patient cord blood and develop a chimeric animal model of inflammatory arthritis using genetically predisposed immune cells.

  16. Minocycline counter-regulates pro-inflammatory microglia responses in the retina and protects from degeneration.

    Science.gov (United States)

    Scholz, Rebecca; Sobotka, Markus; Caramoy, Albert; Stempfl, Thomas; Moehle, Christoph; Langmann, Thomas

    2015-11-17

    Microglia reactivity is a hallmark of retinal degenerations and overwhelming microglial responses contribute to photoreceptor death. Minocycline, a semi-synthetic tetracycline analog, has potent anti-inflammatory and neuroprotective effects. Here, we investigated how minocycline affects microglia in vitro and studied its immuno-modulatory properties in a mouse model of acute retinal degeneration using bright white light exposure. LPS-treated BV-2 microglia were stimulated with 50 μg/ml minocycline for 6 or 24 h, respectively. Pro-inflammatory gene transcription was determined by real-time RT-PCR and nitric oxide (NO) secretion was assessed using the Griess reagent. Caspase 3/7 levels were determined in 661W photoreceptors cultured with microglia-conditioned medium in the absence or presence of minocycline supplementation. BALB/cJ mice received daily intraperitoneal injections of 45 mg/kg minocycline, starting 1 day before exposure to 15.000 lux white light for 1 hour. The effect of minocycline treatment on microglial reactivity was analyzed by immunohistochemical stainings of retinal sections and flat-mounts, and messenger RNA (mRNA) expression of microglia markers was determined using real-time RT-PCR and RNA-sequencing. Optical coherence tomography (OCT) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stainings were used to measure the extent of retinal degeneration and photoreceptor apoptosis. Stimulation of LPS-activated BV-2 microglia with minocycline significantly diminished the transcription of the pro-inflammatory markers CCL2, IL6, and inducible nitric oxide synthase (iNOS). Minocycline also reduced the production of NO and dampened microglial neurotoxicity on 661W photoreceptors. Furthermore, minocycline had direct protective effects on 661W photoreceptors by decreasing caspase 3/7 activity. In mice challenged with white light, injections of minocycline strongly decreased the number of amoeboid alerted microglia in the outer

  17. Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats

    Energy Technology Data Exchange (ETDEWEB)

    Marín-Prida, Javier [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Pavón-Fuentes, Nancy [International Centre for Neurological Restoration (CIREN), Ave. 25 e/ 158 y 160, Playa, PO Box: 11300, Havana (Cuba); Llópiz-Arzuaga, Alexey; Fernández-Massó, Julio R. [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Delgado-Roche, Liván [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Mendoza-Marí, Yssel; Santana, Seydi Pedroso; Cruz-Ramírez, Alieski; Valenzuela-Silva, Carmen; Nazábal-Gálvez, Marcelo; Cintado-Benítez, Alberto [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Pardo-Andreu, Gilberto L. [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Polentarutti, Nadia [Istituto Clinico Humanitas (IRCCS), Rozzano (Italy); Riva, Federica [Department of Veterinary Science and Public Health (DIVET), University of Milano (Italy); Pentón-Arias, Eduardo [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Pentón-Rol, Giselle [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba)

    2013-10-01

    Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24 h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H{sub 2}O{sub 2} and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed. - Highlights: • Phycocyanobilin (PCB) prevents H{sub 2}O{sub 2} and glutamate induced PC12 cell viability loss. • Anterior cortex and striatum are highly vulnerable to cerebral hypoperfusion (CH). • PCB modulates 190 genes associated to inflammation in acute CH. • PCB regulates 19 genes mostly related to a detrimental pro-inflammatory environment. • PCB restores redox and immune balances showing promise as potential stroke therapy.

  18. VEGF receptor antagonist Cyclo-VEGI reduces inflammatory reactivity and vascular leakiness and is neuroprotective against acute excitotoxic striatal insult

    Directory of Open Access Journals (Sweden)

    McLarnon James G

    2008-05-01

    Full Text Available Abstract Background Excitotoxic brain insult is associated with extensive neuronal damage but could also cause inflammatory reactivity and vascular remodeling. The effects of the vascular endothelial growth factor (VEGF inhibitor, Cyclo-VEGI on expression of VEGF, microgliosis and astrogliosis, blood-brain barrier (BBB integrity and neuronal viability have been studied following intra-striatal injection of the excitotoxin, quinolinic acid (QUIN. The purpose of this study was to examine VEGF-dependent inflammatory responses in excitotoxin-injected brain and their dependence on pharmacological antagonism of VEGF receptors. Methods Single and double immunofluorescence staining of cellular (microglia, astrocyte, neuron responses and dye and protein infiltration of blood-brain barrier have been applied in the absence, and presence, of pharmacological modulation using a VEGF receptor antagonist, Cyclo-VEGI. Dunn-Bonferroni statistical analysis was used to measure for significance between animal groups. Results Detailed analysis, at a single time point of 1 d post-QUIN injection, showed excitotoxin-injected striatum to exhibit marked increases in microgliosis (ED1 marker, astrogliosis (GFAP marker and VEGF expression, compared with PBS injection. Single and double immunostaining demonstrated significant effects of Cyclo-VEGI treatment of QUIN-injected striatum to inhibit microgliosis (by 38%, ED1/VEGF (by 42% and VEGF striatal immunoreactivity (by 43%; astrogliosis and GFAP/VEGF were not significantly altered with Cyclo-VEGI treatment. Leakiness of BBB was indicated by infiltration of Evans blue dye and plasma protein fibrinogen into QUIN-injected striatum with barrier permeability restored by 62% (Evans blue permeability and 49% (fibrinogen permeability with Cyclo-VEGI application. QUIN-induced toxicity was demonstrated with loss of striatal neurons (NeuN marker and increased neuronal damage (Fluoro-Jade marker with significant neuroprotection

  19. Ambient particulate air pollution from vehicles promotes lipid peroxidation and inflammatory responses in rat lung.

    Science.gov (United States)

    Pereira, C E L; Heck, T G; Saldiva, P H N; Rhoden, C R

    2007-10-01

    Oxidative stress plays a major role in the pathogenesis of particle-dependent lung injury. Ambient particle levels from vehicles have not been previously shown to cause oxidative stress to the lungs. The present study was conducted to a) determine whether short-term exposure to ambient levels of particulate air pollution from vehicles elicits inflammatory responses and lipid peroxidation in rat lungs, and b) determine if intermittent short-term exposures (every 4 days) induce some degree of tolerance. Three-month-old male Wistar rats were exposed to ambient particulate matter (PM) from vehicles (N = 30) for 6 or 20 continuous hours, or for intermittent (5 h) periods during 20 h for 4 consecutive days or to filtered air (PM polluted air for 20 h (P-20) showed a significant increase in the total number of leukocytes in bronchoalveolar lavage compared to control (C-20: 2.61 x 105 +/- 0.51;P-20: 5.01 x 105 +/- 0.81; P air pollution did not cause a significant increase in lung water content. These data suggest oxidative stress as one of the mechanisms responsible for the acute adverse respiratory effects of particles, and suggest that short-term inhalation of ambient particulate air pollution from street with high automobile traffic represents a biological hazard.

  20. Neuroendocrine modulation of the inflammatory response in common carp: adrenaline regulates leukocyte profile and activity

    NARCIS (Netherlands)

    Kepka, M.; Verburg-van Kemenade, B.M.L.; Chadzinska, M.K.

    2013-01-01

    Inflammatory responses have to be carefully controlled, as high concentrations and/or prolonged action of inflammation-related molecules (e.g. reactive oxygen species, nitric oxide and pro-inflammatory cytokines) can be detrimental to host tissue and organs. One of the potential regulators of the

  1. The Role of Phospholipase C Signaling in Macrophage-Mediated Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Liqian Zhu

    2018-01-01

    Full Text Available Macrophages are crucial members of the mononuclear phagocyte system essential to protect the host from invading pathogens and are central to the inflammatory response with their ability to acquire specialized phenotypes of inflammatory (M1 and anti-inflammatory (M2 and to produce a pool of inflammatory mediators. Equipped with a broad range of receptors, such as Toll-like receptor 4 (TLR4, CD14, and Fc gamma receptors (FcγRs, macrophages can efficiently recognize and phagocytize invading pathogens and secrete cytokines by triggering various secondary signaling pathways. Phospholipase C (PLC is a family of enzymes that hydrolyze phospholipids, the most significant of which is phosphatidylinositol 4,5-bisphosphate [PI(4,5P2]. Cleavage at the internal phosphate ester generates two second messengers, inositol 1,4,5-trisphosphate (IP3 and diacylglycerol (DAG, both of which mediate in diverse cellular functions including the inflammatory response. Recent studies have shown that some PLC isoforms are involved in multiple stages in TLR4-, CD14-, and FcγRs-mediated activation of nuclear factor kappa B (NF-κB, mitogen-activated protein kinase (MAPK, and interferon regulatory factors (IRFs, all of which are associated with the regulation of the inflammatory response. Therefore, secondary signaling by PLC is implicated in the pathogenesis of numerous inflammatory diseases. This review provides an overview of our current knowledge on how PLC signaling regulates the macrophage-mediated inflammatory response.

  2. The Mutyh base excision repair gene influences the inflammatory response in a mouse model of ulcerative colitis.

    Directory of Open Access Journals (Sweden)

    Ida Casorelli

    Full Text Available BACKGROUND: The Mutyh DNA glycosylase is involved in the repair of oxidized DNA bases. Mutations in the human MUTYH gene are responsible for colorectal cancer in familial adenomatous polyposis. Since defective DNA repair genes might contribute to the increased cancer risk associated with inflammatory bowel diseases, we compared the inflammatory response of wild-type and Mutyh(-/- mice to oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: The severity of colitis, changes in expression of genes involved in DNA repair and inflammation, DNA 8-oxoguanine levels and microsatellite instability were analysed in colon of mice treated with dextran sulfate sodium (DSS. The Mutyh(-/- phenotype was associated with a significant accumulation of 8-oxoguanine in colon DNA of treated mice. A single DSS cycle induced severe acute ulcerative colitis in wild-type mice, whereas lesions were modest in Mutyh(-/- mice, and this was associated with moderate variations in the expression of several cytokines. Eight DSS cycles caused chronic colitis in both wild-type and Mutyh(-/- mice. Lymphoid hyperplasia and a significant reduction in Foxp3(+ regulatory T cells were observed only in Mutyh(-/- mice. CONCLUSIONS: The findings indicate that, in this model of ulcerative colitis, Mutyh plays a major role in maintaining intestinal integrity by affecting the inflammatory response.

  3. In vivo electrochemical characterization and inflammatory response of multiwalled carbon nanotube-based electrodes in rat hippocampus

    Science.gov (United States)

    Minnikanti, Saugandhika; Pereira, Marilia G. A. G.; Jaraiedi, Sanaz; Jackson, Kassandra; Costa-Neto, Claudio M.; Li, Qiliang; Peixoto, Nathalia

    2010-02-01

    Stimulating neural electrodes are required to deliver charge to an environment that presents itself as hostile. The electrodes need to maintain their electrical characteristics (charge and impedance) in vivo for a proper functioning of neural prostheses. Here we design implantable multi-walled carbon nanotubes coating for stainless steel substrate electrodes, targeted at wide frequency stimulation of deep brain structures. In well-controlled, low-frequency stimulation acute experiments, we show that multi-walled carbon nanotube electrodes maintain their charge storage capacity (CSC) and impedance in vivo. The difference in average CSCs (n = 4) between the in vivo (1.111 mC cm-2) and in vitro (1.008 mC cm-2) model was statistically insignificant (p > 0.05 or P-value = 0.715, two tailed). We also report on the transcription levels of the pro-inflammatory cytokine IL-1β and TLR2 receptor as an immediate response to low-frequency stimulation using RT-PCR. We show here that the IL-1β is part of the inflammatory response to low-frequency stimulation, but TLR2 is not significantly increased in stimulated tissue when compared to controls. The early stages of neuroinflammation due to mechanical and electrical trauma induced by implants can be better understood by detection of pro-inflammatory molecules rather than by histological studies. Tracking of such quantitative response profits from better analysis methods over several temporal and spatial scales. Our results concerning the evaluation of such inflammatory molecules revealed that transcripts for the cytokine IL-1β are upregulated in response to low-frequency stimulation, whereas no modulation was observed for TLR2. This result indicates that the early response of the brain to mechanical trauma and low-frequency stimulation activates the IL-1β signaling cascade but not that of TLR2.

  4. Pathophysiology of the systemic inflammatory response after major accidental trauma

    DEFF Research Database (Denmark)

    Brøchner, Anne Craveiro; Toft, Palle

    2009-01-01

    and uncomplicated surgery a delicate balance between pro- and anti-inflammatory mediators is observed.Trauma patients are, however, often exposed, not only to the trauma, but to several evens in the form of initial surgery and later final reconstructive surgery. In this case immune paralysis associated...

  5. The response of pre-inflammatory cytokines factors to different ...

    African Journals Online (AJOL)

    Khalid Mohamadzadeh Salamat

    2016-01-23

    Jan 23, 2016 ... Abstract Applying several energy systems and concurrent performing of various training models have a more effective ... concurrent (endurance–resistance) training on pre-inflammatory cytokines in overweight men. Accordingly, 43 healthy ... in pathology of many chronic diseases such as cardiovascular.

  6. Salicornia bigelovii Torr Attenuates Neuro-Inflammatory Responses ...

    African Journals Online (AJOL)

    BV- microglial cells were stimulated with LPS to study the protein expression and production of inflammatory mediators, determined by Western blot analysis. Results: SBE significantly inhibited the DPPH-generated free radicals showing maximum inhibition at 40 μg/mL (p < 0.001). SBE alone did not exhibit any signs of ...

  7. Influência da resposta inflamatória de fase aguda nos níveis séricos de retinol e da proteína de ligação do retinol em pacientes com AIDS Influence of acute-phase inflammatory response on serum levels of retinol and retinol binding protein in HIV/AIDS patients

    Directory of Open Access Journals (Sweden)

    Fábio Fernandes Neves

    2010-02-01

    Full Text Available INTRODUÇÃO: a hiporretinolemia constitui fator prognóstico independente em pacientes com AIDS, e a atividade inflamatória causa redução dos níveis séricos deste nutriente na população em geral. Entretanto, faltam estudos que avaliem o impacto da atividade inflamatória sobre o nível sérico do retinol em pacientes com AIDS. MÉTODOS: foram avaliados transversalmente 41 pacientes internados por complicações da AIDS, que tiveram quantificados alguns marcadores de inflamação (proteína C reativa e fator de necrose tumoral alfa e concentrações séricas de retinol e da proteína de ligação do retinol. RESULTADOS: apesar da baixa (14,6% prevalência de hiporretinolemia evidenciou-se correlação negativa dos marcadores de inflamação com os níveis séricos de retinol e de sua proteína de ligação nos pacientes com AIDS. CONCLUSÕES: a atividade inflamatória de fase aguda está associada a baixos níveis séricos de retinol em indivíduos com AIDS.INTRODUCTION: Hyporetinolemia is an independent prognostic factor in AIDS patients. Inflammatory activity causes a reduction in the serum levels of this nutrient in the general population. However, there are no studies assessing the impact of inflammatory activity on the serum retinol level in AIDS patients. METHODS: A cross-sectional assessment was conducted on 41 patients hospitalized due to AIDS complications. Inflammatory markers (C-reactive protein and tumor necrosis factor-alpha and serum retinol and retinol binding protein concentrations were quantified. RESULTS: Despite the low (14.6% prevalence of hyporetinolemia, a significant negative correlation was observed between the inflammatory markers and the serum retinol and retinol binding protein levels in AIDS patients. CONCLUSIONS: Acute-phase inflammatory activity is associated with low serum retinol levels in individuals with AIDS.

  8. NaV1.9 Potentiates Oxidized Phospholipid-Induced TRP Responses Only under Inflammatory Conditions

    Directory of Open Access Journals (Sweden)

    Corinna Martin

    2018-01-01

    Full Text Available Oxidized phospholipids (OxPL like oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC were recently identified as novel proalgesic targets in acute and chronic inflammatory pain. These endogenous chemical irritants are generated in inflamed tissue and mediate their pain-inducing function by activating the transient receptor potential channels TRPA1 and TRPV1 expressed in sensory neurons. Notably, prototypical therapeutics interfering with OxPL were shown to inhibit TRP channel activation and pain behavior. Here, we asked how OxPL excite primary sensory neurons of dorsal root ganglia (DRG neurons from mice of either sex. Acute stimulation of sensory neurons with the prototypical OxPL 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC evoked repetitive calcium spikes in small-diameter neurons. As NaV1.9, a voltage-gated sodium channel involved in nociceptor excitability, was previously shown to be essential for the generation of calcium spikes in motoneurons, we asked if this channel is also important for OxPL mediated calcium spike and action potential generation in nociceptors. In wild-type and NaV1.9-deficient neurons, the action potential firing rate and the calcium spike frequency to an acute PGPC stimulus was similar. When preincubated with inflammatory mediators, both, the action potential firing rate and the calcium spike frequency were markedly increased in response to an acute PGPC stimulus. However, this potentiating effect was completely lost in NaV1.9-deficient small-diameter neurons. After treatment with inflammatory mediators, the resting membrane potential of NaV1.9 KO neurons was slightly more negative than that of wild-type control neurons. This suggests that NaV1.9 channels are active under this condition and therefore increases the ease with which action potentials are elicited after OxPL stimulation. In summary, our data suggest that NaV1.9 has a switch function to potentiate the receptor potentials

  9. Anti-irritant and anti-inflammatory effects of glycerol and xylitol in sodium lauryl sulphate-induced acute irritation.

    Science.gov (United States)

    Szél, E; Polyánka, H; Szabó, K; Hartmann, P; Degovics, D; Balázs, B; Németh, I B; Korponyai, C; Csányi, E; Kaszaki, J; Dikstein, S; Nagy, K; Kemény, L; Erős, G

    2015-12-01

    Glycerol is known to possess anti-irritant and hydrating properties and previous studies suggested that xylitol may also have similar effects. Our aim was to study whether different concentrations of these polyols restore skin barrier function and soothe inflammation in sodium lauryl sulphate (SLS)-induced acute irritation. The experiments were performed on male SKH-1 hairless mice. The skin of the dorsal region was exposed to SLS (5%) for 3 h alone or together with 5% or 10% of glycerol respectively. Further two groups received xylitol solutions (8.26% and 16.52% respectively) using the same osmolarities, which were equivalent to those of the glycerol treatments. The control group was treated with purified water. Transepidermal water loss (TEWL) and skin hydration were determined. Microcirculatory parameters of inflammation were observed by means of intravital videomicroscopy (IVM). Furthermore, accumulation of neutrophil granulocytes and lymphocytes, the expression of inflammatory cytokines and SLS penetration were assessed, as well. Treatment with the 10% of glycerol and both concentrations of xylitol inhibited the SLS-induced elevation of TEWL and moderated the irritant-induced increase in dermal blood flow and in the number of leucocyte-endothelial interactions. All concentrations of the applied polyols improved hydration and prevented the accumulation of lymphocytes near the treatment site. At the mRNA level, neither glycerol nor xylitol influenced the expression of interleukin-1 alpha. However, expression of interleukin-1 beta was significantly decreased by the 10% glycerol treatment, while expression of tumour necrosis factor-alpha decreased upon the same treatment, as well as in response to xylitol. Higher polyol treatments decreased the SLS penetration to the deeper layers of the stratum corneum. Both of the analysed polyols exert considerable anti-irritant and anti-inflammatory properties, but the effective concentration of xylitol is lower than that of

  10. Derivation of a T2-weighted MRI total colonic inflammation score (TCIS) for assessment of patients with severe acute inflammatory colitis - a preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Hafeez, Rehana; Boulos, Paul [University College London Hospitals NHS Trust, Department of Surgery, London (United Kingdom); Punwani, Shonit; Halligan, Steve [University College London, Centre for Medical Imaging, London (United Kingdom); University College London Hospitals NHS Trust, Department of Specialist X-ray, Level 2 podium, London (United Kingdom); Pendse, Doug [University College London, Centre for Medical Imaging, London (United Kingdom); Bloom, Stuart [University College London Hospitals NHS Trust, Department of Gastroenterology, London (United Kingdom); Taylor, Stuart A. [University College London, Centre for Medical Imaging, London (United Kingdom); University College London Hospitals NHS Trust, Department of Specialist X-ray, Level 2 podium, London (United Kingdom)

    2011-02-15

    To derive an MRI score for assessing severity, therapeutic response and prognosis in acute severe inflammatory colitis. Twenty-one patients with acute severe colitis underwent colonic MRI after admission and again (n = 16) after median 5 days of treatment. Using T2-weighted images, two radiologists in consensus graded segmental haustral loss, mesenteric and mural oedema, mural thickness, and small bowel and colonic dilatation producing a total colonic inflammatory score (TCIS, range 6-95). Pre- and post-treatment TCIS were compared, and correlated with CRP, stool frequency, and number of inpatient days (therapeutic response marker). Questionnaire assessment of patient worry, satisfaction and discomfort graded 1 (bad) to 7 (good) was administered Admission TCIS correlated significantly with CRP (Kendall's tau=0.45, 95% confidence interval [CI] 0.11-0.79, p = 0.006), and stool frequency (Kendall's tau 0.39, 95% CI 0.14-0.64, p = 0.02). TCIS fell after treatment (median [22 range 15-31]) to median 20 [range 8-25], p = 0.01. Admission TCIS but not CRP or stool frequency was correlated with length of inpatient stay (Kendall's tau 0.40, 95% CI 0.11-0.69, p = 0.02). Patients reported some discomfort (median score 4) during MRI. MRI TCIS falls after therapy, correlates with existing markers of disease severity, and in comparison may better predict therapeutic response. (orig.)

  11. The Biochemical Origin of Pain – Proposing a new law of Pain: The origin of all Pain is Inflammation and the Inflammatory Response PART 1 of 3 – A unifying law of pain

    OpenAIRE

    Omoigui, Sota

    2007-01-01

    We are proposing a unifying theory or law of pain, which states: The origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and m...

  12. Anti-Inflammatory Effects of Licorice and Roasted Licorice Extracts on TPA-Induced Acute Inflammation and Collagen-Induced Arthritis in Mice

    Directory of Open Access Journals (Sweden)

    Ki Rim Kim

    2010-01-01

    Full Text Available The anti-inflammatory activity of licorice (LE and roated licorice (rLE extracts determined in the murine phorbol ester-induced acute inflammation model and collagen-induced arthritis (CIA model of human rheumatoid arthritis. rLE possessed greater activity than LE in inhibiting phorbol ester-induced ear edema. Oral administration of LE or rLE reduced clinical arthritis score, paw swelling, and histopathological changes in a murine CIA. LE and rLE decreased the levels of proinflammatory cytokines in serum and matrix metalloproteinase-3 expression in the joints. Cell proliferation and cytokine secretion in response to type II collagen or lipopolysaccharide stimulation were suppressed in spleen cells from LE or rLE-treated CIA mice. Furthermore, LE and rLE treatment prevented oxidative damages in liver and kidney tissues of CIA mice. Taken together, LE and rLE have benefits in protecting against both acute inflammation and chronic inflammatory conditions including rheumatoid arthritis. rLE may inhibit the acute inflammation more potently than LE.

  13. Melatonin does not affect oxidative/inflammatory biomarkers in a closed-chest porcine model of acute myocardial infarction

    DEFF Research Database (Denmark)

    Halladin, Natalie L.; Busch, Sarah Victoria Ekeløf; Jensen, Svend Eggert

    2014-01-01

    AIM: To test whether melatonin reduces oxidative and inflammatory biomarkers in a closed-chest porcine model of acute myocardial infarction. MATERIALS AND METHODS: Twenty pigs were randomized to receive a total dosage of 200 mg (0.4 mg/ml) of melatonin, or placebo immediately prior to reperfusion....... There was an increase in hs-TnT, but no significant difference between the melatonin-treated and placebo-treated groups. There were no significant differences in development of any of the circulating plasma markers between the two groups. CONCLUSION: Melatonin treatment did not result in reduction of inflammatory...

  14. Melatonin Does Not Affect Oxidative/Inflammatory Biomarkers in a Closed-Chest Porcine Model of Acute Myocardial Infarction

    DEFF Research Database (Denmark)

    Halladin, Natalie L.; Ekelof, Sarah; Jensen, Svend Eggert

    2014-01-01

    Aim: To test whether melatonin reduces oxidative and inflammatory biomarkers in a closed-chest porcine model of acute myocardial infarction. Materials and Methods: Twenty pigs were randomized to receive a total dosage of 200 mg (0.4 mg/ml) of melatonin, or placebo immediately prior to reperfusion....... There was an increase in hs-TnT, but no significant difference between the melatonin-treated and placebo-treated groups. There were no significant differences in development of any of the circulating plasma markers between the two groups. Conclusion: Melatonin treatment did not result in reduction of inflammatory...

  15. ANTIOXIDANT SUPPLEMENTATION AND NASAL INFLAMMATORY RESPONSES AMONG YOUNG ASTHMATICS EXPOSED TO HIGH LEVELS OF OZONE

    Science.gov (United States)

    Background: Recent studies examining the inflammatory response in atopic asthma to ozone suggest a release of soluble mediators of inflammation factors that might be related to reactive oxygen species (ROS). Antioxidant could prove useful in subjects exposed to additional oxidati...

  16. Increased inflammatory response and neovascularization in reperfused vs. nonreperfused murine myocardial infarction

    NARCIS (Netherlands)

    Vandervelde, S; van Amerongen, MJ; Tio, RA; Petersen, AH; van Luyn, MJA; Harmsen, MC

    2006-01-01

    Introduction: Fundamental knowledge of the inflammatory response after myocardial infarction (MI) is indispensable for intervention toward cardiac regeneration. Although reperfusion is preferred as clinical therapy, for basic research, also permanent ligation MI models are widely used. Methods: In

  17. Carbon monoxide-bound hemoglobin vesicles ameliorate multiorgan injuries induced by severe acute pancreatitis in mice by their anti-inflammatory and antioxidant properties.

    Science.gov (United States)

    Nagao, Saori; Taguchi, Kazuaki; Sakai, Hiromi; Yamasaki, Keishi; Watanabe, Hiroshi; Otagiri, Masaki; Maruyama, Toru

    Carbon monoxide (CO) has attracted attention as a possible therapeutic agent for affecting anti-inflammatory and antioxidant activities. Previously, CO-bound hemoglobin vesicle (CO-HbV) was developed as a nanotechnology-based CO donor, and its safety profile and therapeutic potential as a clinically applicable carrier of CO were examined in vitro and in vivo. In the present study, the therapeutic efficacy of CO-HbV against severe acute pancreatitis was examined with secondary distal organ-injured model mice that were fed with a choline-deficient ethionine-supplemented diet. A CO-HbV treatment significantly reduced the mortality of the acute pancreatitis model mice compared to saline and HbV. Biochemical and histological evaluations clearly showed that CO-HbV suppressed acute pancreatitis by inhibiting the production of systemic proinflammatory cytokines, neutrophil infiltration, and oxidative injuries in pancreatic tissue. Interestingly, CO-HbV also diminished the subsequent damage to distal organs including liver, kidneys, and lungs. This could be due to the suppression of neutrophil infiltration into tissues and the subsequently enhanced oxidative injuries. In contrast, O 2 -bound HbV, the inactive form of CO-HbV, was ineffective against both pancreatitis and distal organ injuries, confirming that CO was directly responsible for the protective effects of CO-HbV in acute pancreatitis. These findings suggest that CO-HbV has anti-inflammatory and antioxidant characteristics of CO and consequently exerts a superior protective effect against acute pancreatitis-induced multiorgan damage.

  18. The Response of Macrophages and Neutrophils to Hypoxia in the Context of Cancer and Other Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Antje Egners

    2016-01-01

    Full Text Available Lack of oxygen (hypoxia is a hallmark of a multitude of acute and chronic diseases and can be either beneficial or detrimental for organ restitution and recovery. In the context of inflammation, hypoxia is particularly important and can significantly influence the course of inflammatory diseases. Macrophages and neutrophils, the chief cellular components of innate immunity, display distinct properties when exposed to hypoxic conditions. Virtually every aspect of macrophage and neutrophil function is affected by hypoxia, amongst others, morphology, migration, chemotaxis, adherence to endothelial cells, bacterial killing, differentiation/polarization, and protumorigenic activity. Prominent arenas of macrophage and neutrophil function, for example, acute/chronic inflammation and the microenvironment of solid tumors, are characterized by low oxygen levels, demonstrating the paramount importance of the hypoxic response for proper function of these cells. Members of the hypoxia-inducible transcription factor (HIF family emerged as pivotal molecular regulators of macrophages and neutrophils. In this review, we will summarize the molecular responses of macrophages and neutrophils to hypoxia in the context of cancer and other chronic inflammatory diseases and discuss the potential avenues for therapeutic intervention that arise from this knowledge.

  19. Biological response modifiers and their potential use in the treatment of inflammatory skin diseases

    DEFF Research Database (Denmark)

    Villadsen, Louise S; Skov, Lone; Baadsgaard, Ole

    2003-01-01

    In recent years, a more detailed understanding of the pathogenesis of several inflammatory skin diseases, combined with the developments within biotechnology, has made it possible to design more selective response modifiers. Biological response modifiers hold the potential for greater effectivene......, recombinant cytokines, or fusion proteins may be effective. Several biological response modifiers have already shown positive results in phase II/III clinical trials in skin diseases, and many new biological response modifiers are in progress.......In recent years, a more detailed understanding of the pathogenesis of several inflammatory skin diseases, combined with the developments within biotechnology, has made it possible to design more selective response modifiers. Biological response modifiers hold the potential for greater effectiveness...... and fewer side-effects than the current systemic therapies now used for severe psoriasis, contact dermatitis and atopic dermatitis. In the pathogenesis of inflammatory skin diseases, the immune system plays a pivotal role, and this is where biological response modifiers such as monoclonal antibodies...

  20. Citral reduces nociceptive and inflammatory response in rodents

    Directory of Open Access Journals (Sweden)

    Lucindo J. Quintans-Júnior

    2011-04-01

    Full Text Available Citral (CIT, which contains the chiral enantiomers, neral (cis and geranial (trans, is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001 against acetic acid (0.8% induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05 only at higher dose (200 mg/kg of CIT in the first phase of the test. CIT significantly reduce (p<0.001 nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg significantly reduced (p<0.001 the leukocyte migration in the carrageenan-induced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

  1. Citral reduces nociceptive and inflammatory response in rodents

    Directory of Open Access Journals (Sweden)

    Lucindo J. Quintans-Júnior

    2011-06-01

    Full Text Available Citral (CIT, which contains the chiral enantiomers, neral (cis and geranial (trans, is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001 against acetic acid (0.8% induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05 only at higher dose (200 mg/kg of CIT in the first phase of the test. CIT significantly reduce (p<0.001 nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg significantly reduced (p<0.001 the leukocyte migration in the carrageenan-induced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

  2. Enhanced expression and activation of pro-inflammatory transcription factors distinguish aneurysmal from atherosclerotic aorta: IL-6- and IL-8-dominated inflammatory responses prevail in the human aneurysm

    NARCIS (Netherlands)

    Lindeman, J.H.N.; Abdul-Hussien, H.; Schaapherder, A.F.M.; Bockel, J.H. van; Thüsen, J.H. vonder; Roelen, D.L.; Kleemann, R.

    2008-01-01

    Inflammation plays a key role in the pathogenesis of an AAA (abdominal aortic aneurysm); however, the nature of the inflammatory factors and cellular response(s) involved in AAA growth is controversial. In the present study, we set out to determine the aortic levels of inflammatory cytokines in

  3. Ginger Extract Suppresses Inflammatory Response and Maintains Barrier Function in Human Colonic Epithelial Caco-2 Cells Exposed to Inflammatory Mediators.

    Science.gov (United States)

    Kim, Yunyoung; Kim, Dong-Min; Kim, Ji Yeon

    2017-05-01

    The beneficial effects of ginger in the management of gastrointestinal disturbances have been reported. In this study, the anti-inflammatory potential of ginger extract was assessed in a cellular model of gut inflammation. In addition, the effects of ginger extract and its major active compounds on intestinal barrier function were evaluated. The response of Caco-2 cells following exposure to a mixture of inflammatory mediators [interleukin [IL]-1β, 25 ng/mL; lipopolysaccharides [LPS], 10 ng/mL; tumor necrosis factor [TNF]-α, 50 ng/mL; and interferon [INF]-γ, 50 ng/mL] were assessed by measuring the levels of secreted IL-6 and IL-8. In addition, the mRNA levels of cyclooxygenase-2 and inducible nitric oxide synthase were measured. Moreover, the degree of nuclear factor (NF)-κB inhibition was examined, and the intestinal barrier function was determined by measuring the transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC)-dextran transfer. It was observed that ginger extract and its constituents improved inflammatory responses by decreasing the levels of nitrite, PGE2, IL-6, and IL-8 via NF-κB inhibition. The ginger extract also increased the TEER and decreased the transfer of FITC-dextran from the apical side of the epithelium to the basolateral side. Taken together, these results show that ginger extract may be developed as a functional food for the maintenance of gastrointestinal health. © 2017 Institute of Food Technologists®.

  4. Differential role of tumor necrosis factor receptors in mouse brain inflammatory responses in cryolesion brain injury

    DEFF Research Database (Denmark)

    Quintana, Albert; Giralt, Mercedes; Rojas, Santiago

    2005-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via...... by TNFR1 deficiency. Overall, these results suggest that TNFR1 is involved in the early establishment of the inflammatory response and that its deficiency causes a decreased inflammatory response and tissue damage following brain injury....

  5. A Comparison of the Inflammatory Response Produced by Commercial Eugenol and Purified Eugenol,

    Science.gov (United States)

    1980-05-22

    irritant. However, commercial or "stock" eugenol contains a number of impurities; 20,21 e.g. acetyl eugenol , furfurai, methyl -n-amyl-ketone, and others...block nmber) Eugenol is one of the major therapeutic agents In dentistry. The inflammatory.0 response to purified and commercial eugenol are compared...and the Inflammatory C response to zinc oxide/ eugenol prepared with either purified’or commercial eugenol are also compared. The results indicate

  6. Accelerated superfractionated radiotherapy for inflammatory breast carcinoma: complete response predicts outcome and allows for breast conservation

    International Nuclear Information System (INIS)

    Arthur, Douglas W.; Schmidt-Ullrich, Rupert K.; Friedman, Richard B.; Wazer, David E.; Kachnic, Lisa A.; Amir, Cyrus; Bear, Harry D.; Hackney, Mary Helen; Smith, Thomas J.; Lawrence, Walter

    1999-01-01

    Purpose: Chemotherapy and accelerated superfractionated radiotherapy were prospectively applied for inflammatory breast carcinoma with the intent of breast conservation. The efficacy, failure patterns, and patient tolerance utilizing this approach were analyzed. Methods and Materials: Between 1983 and 1996, 52 patients with inflammatory breast carcinoma presented to the Medical College of Virginia Hospitals of VCU and the New England Medical Center. Thirty-eight of these patients were jointly evaluated in multidisciplinary breast clinics and managed according to a defined prospectively applied treatment policy. Patients received induction chemotherapy, accelerated superfractionated radiotherapy, selected use of mastectomy, and concluded with additional chemotherapy. The majority were treated with 1.5 Gy twice daily to field arrangements covering the entire breast and regional lymphatics. An additional 18-21 Gy was then delivered to the breast and clinically involved nodal regions. Total dose to clinically involved areas was 63-66 Gy. Following chemoradiotherapy, patients were evaluated with physical examination, mammogram, and fine needle aspiration x 3. Mastectomy was reserved for those patients with evidence of persistent or progressive disease in the involved breast. All patients received additional chemotherapy. Results: Median age was 51 years. Median follow-up was 23.9 months (6-86) months. The breast preservation rate at the time of last follow-up was 74%. The treated breast or chest wall as the first site of failure occurred in only 13%, and the ultimate local control rate with the selected use of mastectomy was 74%. Ten patients underwent mastectomy, 2 of which had pathologically negative specimens despite a clinically palpable residual mass. Response to chemotherapy was predictive of treatment outcome. Of the 15 patients achieving a complete response, 87% remain locoregionally controlled without the use of mastectomy. Five-year overall survival for

  7. [SIRS (systemic inflammatory response syndrome): clinical entity, definitions, and the significance].

    Science.gov (United States)

    Kushimoto, S; Yamamoto, Y

    1999-01-01

    The clinical entity, definitions, and the significance of SIRS (systemic inflammatory response syndrome) were reviewed. The term, SIRS was proposed to define sepsis and its sequelae clearly in 1991, in order to make early detection of the disease possible, and to improve the ability to compare innovative potential diagnostic and therapeutic modalities by standardizing terms. Although the criteria of SIRS is not strict and too sensitive, SIRS has been shown to be useful as a warning sign of severe condition in clinical setting. We also discussed about a new concept, CARS (compensatory anti-inflammatory response syndrome), which was characterized as anti-inflammatory mediators-dominant condition, in this issue.

  8. Lyn regulates inflammatory responses in Klebsiella pneumoniae infection via the p38/NF-κB pathway.

    Science.gov (United States)

    Li, Xuefeng; Zhou, Xikun; Ye, Yan; Li, Yi; Li, Jiaxin; Privratsky, Breanna; Wu, Erxi; Gao, Hongwei; Huang, Canhua; Wu, Min

    2014-03-01

    Klebsiella pneumoniae (Kp) is one of the most common pathogens in nosocomial infections and is becoming increasingly multidrug resistant. However, the underlying molecular pathogenesis of this bacterium remains elusive, limiting the therapeutic options. Understanding the mechanism of its pathogenesis may facilitate the development of anti-bacterial therapeutics. Here, we show that Lyn, a pleiotropic Src tyrosine kinase, is involved in host defense against Kp by regulating phagocytosis process and simultaneously downregulating inflammatory responses. Using acute infection mouse models, we observed that lyn(-/-) mice were more susceptible to Kp with increased mortality and severe lung injury compared with WT mice. Kp infected-lyn(-/-) mice exhibited elevated inflammatory cytokines (IL-6 and TNF-α), and increased superoxide in the lung and other organs. In addition, the phosphorylation of p38 and NF-κB p65 subunit increased markedly in response to Kp infection in lyn(-/-) mice. We also demonstrated that the translocation of p65 from cytoplasm to nuclei increased in cultured murine lung epithelial cells by Lyn siRNA knockdown. Furthermore, lipid rafts clustered with activated Lyn and accumulated in the site of Kp invasion. Taken together, these findings revealed that Lyn may participate in host defense against Kp infection through the negative modulation of inflammatory cytokines. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Predictive risk factors for systemic inflammatory response syndrome following ureteroscopic laser lithotripsy.

    Science.gov (United States)

    Uchida, Yusuke; Takazawa, Ryoji; Kitayama, Sachi; Tsujii, Toshihiko

    2017-07-10

    The objective of this study was to investigate risk factors for the development of systemic inflammatory response syndrome following ureteroscopic laser lithotripsy. We retrospectively collected data of 469 patients who underwent ureteroscopic laser lithotripsy at our single institution from February 2008 to June 2016. Details for the patient, the stone, and the surgical factors that potentially contributed to postoperative infection were extracted. Using a logistic regression model, we analyzed how the clinical factors affected the incidence of systemic inflammatory response syndrome. Twenty-seven patients (5.7%) were postoperatively diagnosed with systemic inflammatory response syndrome; of these, 25 patients were diagnosed within 24 h after ureteroscopy. One patient required intensive care unit admission, but no death was reported. A preoperative stent was significantly associated with postoperative systemic inflammatory response syndrome only on univariate analysis, and the reasons for stenting were varied. Multivariate analysis revealed that obstructive pyelonephritis, a positive preoperative bladder urine culture result, and female gender were significantly associated with postoperative systemic inflammatory response syndrome. Patients who experienced obstructive pyelonephritis preceding ureteroscopic laser lithotripsy or had a positive preoperative bladder urine culture result were at an increased risk of systemic inflammatory response syndrome despite receiving appropriate preoperative antibiotic therapy. Regarding the impact of a preoperative stent on postoperative infection, further investigation focusing on reasons for stenting is needed.

  10. Common mechanism in endothelin-3 and PAF receptor function for anti-inflammatory responses.

    Science.gov (United States)

    Sato, Akira; Ebina, Keiichi

    2013-10-15

    Platelet-activating factor (PAF) is a potent lipid mediator that is implicated in numerous inflammatory diseases. Under inflammatory conditions, PAF is biosynthesized through the remodelling pathway and elicits many inflammatory responses through binding to its specific PAF receptor. Endogenous bioactive endothelins (ETs: ET-1, -2, and -3) are also considered potent inflammatory mediators that play a critical role in many inflammatory diseases. In this perspective, we provide a brief overview of possible common mechanisms in ETs and PAF receptor function for inflammatory responses. Accumulating evidence strongly suggests that ET-3, but not ET-1 and ET-2, can attenuate PAF-induced inflammation through direct binding of the Tyr-Lys-Asp (YKD) region in the peptide to PAF and its metabolite/precursor lyso-PAF, followed by inhibition of binding between PAF and its receptor. Additionally, YKD sequence-containing peptides may be useful as a novel type of anti-inflammatory drugs targeting this mechanism. These findings should lead to new treatment strategies for numerous inflammatory diseases by targeting the common mechanism in ET and PAF receptor function. © 2013 Elsevier B.V. All rights reserved.

  11. PEGylated polyplex with optimized PEG shielding enhances gene introduction in lungs by minimizing inflammatory responses.

    Science.gov (United States)

    Uchida, Satoshi; Itaka, Keiji; Chen, Qixian; Osada, Kensuke; Ishii, Takehiko; Shibata, Masa-Aki; Harada-Shiba, Mariko; Kataoka, Kazunori

    2012-06-01

    Safety is a critical issue in clinical applications of nonviral gene delivery systems. Safe and effective gene introduction into the lungs was previously achieved using polyplexes from poly(ethyleneglycol) (PEG)-block-polycation [PEG-block-PAsp(DET)] and plasmid DNA (pDNA). Although PEGylated polyplexes appeared to be safe, an excess ratio of polycation to pDNA was needed to obtain sufficient transgene expression, which may cause toxicities shortly after gene introduction. In the present study, we investigated the combined use of two polymers, PEG-block-PAsp(DET) (B) and homo PAsp(DET) (H) across a range of mixing ratios to construct polyplexes. Although transgene expressions following in vitro transfections increased in parallel with increased proportions of H, polyplexes with B/H = 50/50 formulation produced the highest expression level following in vivo intratracheal administration. Higher proportions of H elicited high levels of cytokine induction with significant inflammation as assessed by histopathological examinations. Based on the aggregation behavior of polyplexes in bronchoalveolar lavage fluids (BALFs), we suggested that rapid aggregation of polyplexes in the lung induced acute inflammatory responses, resulting in reduced transgene expression. B/H formulation of polyplex can help to improve gene therapy for the respiratory system because it achieves both effective PEG shielding of polyplexes and functioning of PAsp(DET) polycations to enhance endosomal escape.

  12. [A prospective study for systemic inflammatory response syndrome (SIRS) after cerebral infarction].

    Science.gov (United States)

    Xue, Yuan-yuan; Xu, Xiao-yun; Li, Gang; Wang, Yue

    2008-12-01

    To investigate whether systemic inflammatory response syndrome (SIRS) after cerebral infarction is associated with poor outcome and its associated clinical factors. We prospectively studied 500 patients with cerebral infarction, recorded the associated clinical factors on presentation and calculated the mortality at 21st day. There are 85 SIRS patients in 500 patients with cerebral infarction, 31 with total anterior cerebral infarction (TACI), 34 with partial anterior cerebral infarction (PACI), 15 with posterior cerebral infarction (POCI) and 5 with lacunar cerebral infarction (LACI). The frequency of SIRS was positively correlated with mortality rate according to Oxfordshire Community Stroke Project (OCSP) subtypes in cerebral infarction patients with fever (Spearman correlation coefficient = 1.0; P SIRS and mortality of cerebral infarction were as follows: age, infection, 48 h Chinese Stroke Scale score, 48 h Glasgow score, OCSP subtypes and dysphagia. Diabetes was the risk factor for SIRS, but had no effect on mortality. On Cox regression, 48 h Glasgow score was the sole independent risk factor of outcome. However, if SIRS was included in the formula, P > 0.05. SIRS is the predictor of poor outcome after acute cerebral infarction. It is important to prevent SIRS especially in TACI and POCI. Diabetes is the risk factor for SIRS, but has no effect on mortality.

  13. Changes in Serum Acute Phase Reactants, Inflammatory Mediators and Gangliosides in Japanese quail (Coturnix japonica with Retained Yolk Sac

    Directory of Open Access Journals (Sweden)

    N. Mosleh, S. Nazifi* and A. Alaeddini

    2012-05-01

    Full Text Available Twenty-two 2-week-old Japanese quails (Coturnix japonica with retained yolk sac have been assessed using validated standard procedures to quantify the serum concentration of the acute phase reactants (haptoglobin and serum amyloid A, inflammatory mediators (tumor necrosis factor-alpha, gamma interferon and gangliosides (total sialic acid, lipid bound sialic acid and protein bound sialic acid. The present findings show that the concentrations of all measured parameters in diseased birds were significantly higher than the control group. Inflammation following yolk sac infection/retention leads to stimulation of the synthesis of inflammatory mediators, acute phase reactants and gangliosides. Among the study variables, lipid bound sialic acid had the most obvious change, so it is the most sensitive parameter.

  14. Non-HTLV-I associated pleomorphic T-cell lymphoma of the brain mimicking post-vaccinal acute inflammatory demyelination.

    Science.gov (United States)

    Wanschitz, J; Hainfellner, J A; Simonitsch, I; Schnizer, M; Deisenhammer, E; Terunuma, H; Iwasaki, Y; Budka, H

    1997-02-01

    Two weeks after vaccination against tick-borne encephalitis (TBE), a 57-year-old female suddenly developed mental confusion and hemiparesis of the left side. Cranial MRI demonstrated extensive bilateral lesions in the fronto-parietal white matter of both hemispheres, suggesting an acute inflammatory demyelinating disease following vaccination. Despite administration of high-dose corticosteroids, the patient died 3 weeks after onset of neurological symptoms. Autopsy revealed diffuse infiltrates of a primary cerebral pleomorphic T-cell lymphoma of medium and large cell type. PCR on brain tissue for HTLV-I and serology for anti-HTLV-I antibodies in CSF and serum were negative; immunocytochemistry on brain tissue did not detect EBV-related antigen. This is the first recorded observation of a diffusely infiltrating primary central nervous system T-cell lymphoma, clinically and radiologically mimicking a fatal acute inflammatory demyelinating complication after vaccination.

  15. VARIABILITY OF LEUKOCYTE COUNT AS AN INFLAMMATORY RESPONSE AMONG HYPERTENSIVES

    Directory of Open Access Journals (Sweden)

    Brinda

    2015-12-01

    Full Text Available INTRODUCTION Hypertension, a globally prevailing non communicable disease has been linked to various pathophysiological mechanisms. The new spotlight is on the inflammatory mechanism, which has been embarked on this study by utilising the White blood cell counts as the predominant marker. The pathogenesis behind this concept is the endothelial alteration which occurs in hypertension, causing increased oxidative stress and release of inflammatory mediators and further causing damage to the vascular walls and may result in sustained hypertension. OBJECTIVE To substantiate the difference in leukocyte count among the hypertensives and normotensives, to assess the variation in the leukocyte count among varied grades of hypertension. METHODS 80 subjects and 40 controls of both sex and age between 20-60 years were taken. Subjects with other chronic medical disorders, pregnancy, menstruation phase, history of infections in past 3 months, obesity, smokers and regular alcoholics were excluded. Three recordings of blood pressure were measured with a standard mercury sphygmomanometer. The differential leukocyte count was estimated with an automated counter. RESULTS Statistical analysis was done using independent sample t-test and one-way ANOVA. Total Leukocyte count (Mean = 8397.50 ± 1666.57 was raised significantly among the hypertensives, with P value <0.001. Comparison was done on the total count with the varied hypertensive years, which was suggestive of increase in total count among the pre hypertensives (systolic pressure and there was linear increase in total count with diastolic pressure though not statistically significant. CONCLUSION The elevation of white blood cell count is suggestive of underlying inflammatory mechanism among the hypertensives. The onset of inflammation could be at the onset of hypertension, as there is rise in total leukocyte count among the pre hypertensives which could also lead to sustained hypertension.

  16. Dyadic confirmatory factor analysis of the inflammatory bowel disease family responsibility questionnaire.

    Science.gov (United States)

    Greenley, Rachel Neff; Reed-Knight, Bonney; Blount, Ronald L; Wilson, Helen W

    2013-09-01

    Evaluate the factor structure of youth and maternal involvement ratings on the Inflammatory Bowel Disease Family Responsibility Questionnaire, a measure of family allocation of condition management responsibilities in pediatric inflammatory bowel disease. Participants included 251 youth aged 11-18 years with inflammatory bowel disease and their mothers. Item-level descriptive analyses, subscale internal consistency estimates, and confirmatory factor analyses of youth and maternal involvement were conducted using a dyadic data-analytic approach. Results supported the validity of 4 conceptually derived subscales including general health maintenance, social aspects, condition management tasks, and nutrition domains. Additionally, results indicated adequate support for the factor structure of a 21-item youth involvement measure and strong support for a 16-item maternal involvement measure. Additional empirical support for the validity of the Inflammatory Bowel Disease Family Responsibility Questionnaire was provided. Future research to replicate current findings and to examine the measure's clinical utility is warranted.

  17. Intestinal anti-inflammatory activity of ellagic acid in the acute and chronic dextrane sulfate sodium models of mice colitis.

    Science.gov (United States)

    Marín, Marta; María Giner, Rosa; Ríos, José-Luis; Recio, María Carmen

    2013-12-12

    Pomegranate (Punica granatum L.; Lythraceae) has traditionally been used for the treatment of various inflammatory diseases, including ulcerative colitis (UC). Because its fruits and extracts are rich in ellagitannins, which release ellagic acid when hydrolyzed, consumption of pomegranate products is currently being widely promoted for their potential health effects, including the prevention of inflammatory diseases and cancer. To evaluate the anti-inflammatory effects of ellagic acid on dextran sulfate sodium (DSS)-induced acute and chronic experimental colitis in two different strains of mice and to elucidate its possible mechanisms of action. In the acute UC model, female Balb/C mice were treated with DSS (5%) for seven days while concomitantly receiving a dietary supplement of ellagic acid (2%). In the chronic UC model, female C57BL/6 mice received four week-long cycles of DSS (1% and 2%) interspersed with week-long recovery periods along with a diet supplemented with ellagic acid (0.5%). In acute model of UC, ellagic acid ameliorated disease severity slightly as observed both macroscopically and through the profile of inflammatory mediators (IL-6, TNF-α, and IFN-γ). In the chronic UC model, ellagic acid significantly inhibited the progression of the disease, reducing intestinal inflammation and decreasing histological scores. Moreover, mediators such as COX-2 and iNOS were downregulated and the signaling pathways p38 MAPK, NF-κB, and STAT3 were blocked. Our study reinforces the hypothetical use of ellagic acid as an anti-inflammatory complement to conventional UC treatment in chronic UC patients and could be considered in the dietary prevention of intestinal inflammation and related cancer development. © 2013 Published by Elsevier Ireland Ltd.

  18. Acute inflammatory demyelinating polyneuropathy associated with pegylated interferon α 2a therapy for chronic hepatitis C virus infection

    OpenAIRE

    Khiani, Vijay; Kelly, Thomas; Shibli, Adeel; Jensen, Donald; Mohanty, Smruti R

    2008-01-01

    The combination of pegylated interferon (Peg-IFN) and ribavirin is the standard of care for chronic hepatitis C virus (HCV) infection treatment. In general, common side effects related to this combination therapy are mild and are very well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to Peg-IFN is extremely rare. We present the first case of an acute inflammatory demyelinating polyneuropathy (AIDP) associated with Peg-IFN-α 2a (Pegasys) after 16 wk ...

  19. Neutralizing effects of polyvalent antivenom on severe inflammatory response induced by Mesobuthus eupeus scorpion venom

    Directory of Open Access Journals (Sweden)

    Zayerzadeh1 E.

    2014-11-01

    Full Text Available This study evaluated the effects of Mesobuthus eupeus (Me scorpion venom on inflammatory response following injection. Additionally, the present study examined whether immunotherapy at specific time intervals would be effective on inflammatory response after Me venom inoculation. Animals were divided randomly into four groups: the first group received LD50 of venom and the second and third groups of animals; immunotherapy was performed in different time intervals and fourth group was considered as control group. Me venom inoculation is caused respiratory perturbations such as respiratory distress, respiration with open mouth, crepitation and finally respiratory arrest. Me inoculation is resulted in increased pro-inflammatory cytokines including TNF-α and IL-1. Venom injection also induced inflammatory response, characterized by significant increase in serum white blood cells and neutrophils at 30, 60 and 180 min following envenomation. Simultaneous administration of antivenom and venom prevented entirely clinical sings, cytokines and hematological changes. Delayed immunotherapy gradually ameliorated clinical features, cytokines changes and hematological abnormalities related to the envenomation. In conclusion, our observations indicate injection of M. eupeus scorpion venom induces severe inflammatory response which can be one of the causes of clinical complications. Additionally, immunotherapy beyond 1 h after envenomation with appropriate dose and route in victims with severe inflammatory response related to the M.eupeus scorpion envenomation is beneficial.

  20. Functional Food Targeting the Regulation of Obesity-Induced Inflammatory Responses and Pathologies

    Directory of Open Access Journals (Sweden)

    Shizuka Hirai

    2010-01-01

    Full Text Available Obesity is associated with a low-grade systemic chronic inflammatory state, characterized by the abnormal production of pro- and anti-inflammatory adipocytokines. It has been found that immune cells such as macrophages can infiltrate adipose tissue and are responsible for the majority of inflammatory cytokine production. Obesity-induced inflammation is considered a potential mechanism linking obesity to its related pathologies, such as insulin resistance, cardiovascular diseases, type-2 diabetes, and some immune disorders. Therefore, targeting obesity-related inflammatory components may be a useful strategy to prevent or ameliorate the development of such obesity-related diseases. It has been shown that several food components can modulate inflammatory responses in adipose tissue via various mechanisms, some of which are dependent on peroxisome proliferator-activated receptor γ (PPARγ, whereas others are independent on PPARγ, by attenuating signals of nuclear factor-κB (NF-κB and/or c-Jun amino-terminal kinase (JNK. In this review, we introduce the beneficial effects of anti-inflammatory phytochemicals that can help prevent obesity-induced inflammatory responses and pathologies.

  1. Non-Steroid Anti-Inflammatory Drugs Are Better than Acetaminophen on Fever Control at Acute Stage of Fracture.

    Directory of Open Access Journals (Sweden)

    Kuang-Ting Yeh

    Full Text Available In addition to adequate surgical fixation and an aggressive rehabilitation program, pain relief is one of the most critical factors in the acute stage of fracture treatment. The most common analgesics are nonsteroid anti-inflammatory drugs and Acetaminophen, both of which relieve pain and reduce body temperature. In clinical experiences, they exhibit effective pain control; however, their influence on body temperature remains controversial. This study is aimed at determining the effects of analgesics at the acute stage of traumatic fracture by performing a clinical retrospective study of patients with fractures and a fracture animal model. The retrospective study revealed that, in the acetaminophen group, the mean value of postmedication body temperature (BT was significantly higher than that of the premedication BT. The change in BT was highly related with the medication rather than other risk factors. Forty eight 12-week-old male Wistar rats were divided into 6 groups: a control group, fracture group, fracture-Acetaminophen group, Acetaminophen group, fracture-Arcoxia group, and Arcoxia group. Fracture rats were prepared by breaking their unilateral tibia and fibula. Their inflammation conditions were evaluated by measuring their serum cytokine level and their physiological status was evaluated by estimating their central temperature, heart rate, and mean blood pressure. The hepatic adverse effects were assessed by measuring the serum levels of aspartate aminotransferase (sGOT and alanine aminotransferase (sGPT. The central temperature in the fracture-Acetaminophen group exceeded that in the groups fed normal saline water or Arcoxia. Accumulated hepatic injury was presented as steadily ascending curves of sGOT and sGPT. Inflammation-related cytokine levels were not higher in the Acetaminophen fracture group and were significantly lower in the fracture-Arcoxia group. Fever appeared to be aggravated by acetaminophen and more related to the

  2. Polymorphism of the genes of pro-and anti-inflammatory cytocins and acute bronchitis in children

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    O. I. Pikuza

    2017-01-01

    Full Text Available Certain role in the development of respiratory diseases is played by cytokines that possess both pro-and anti-inflammatory activity, and the balance of these factors influences the course of the disease. As shown by studies in recent years, the negative influence of environmental factors, as a rule, implemented against the background of the individual genetic predisposition in virtually any known to date pathology. Objective research: to identify molecular genetic risk factors for the development of acute bronchitis and community-acquired pneumonia in children on the basis of the analysis of polymorphisms of pro- and anti-inflammatory interleukins. A complex clinicallaboratory and instrumental examination of 110 children aged 6 to 15 years with acute bronchitis (the main group was carried out. The control group included 163 conditionally healthy children of the same age. Significant differences were revealed by the polymorphism of the TNFA gene, which has pro-inflammatory properties. At the same time, analysis of the frequency allocation of alleles and genotypes of polymorphism (-174C/G of IL6 and + 3953C/T gene IL1B did not reveal significant differences with the control. The results of the study can be used in the development of prognostic markers of acute pathology in children and optimization of treatment tactics and preventive measures with an individual approach for each patient.

  3. Caspase-12 and the inflammatory response to Yersinia pestis.

    Science.gov (United States)

    Ferwerda, Bart; McCall, Matthew B B; de Vries, Maaike C; Hopman, Joost; Maiga, Boubacar; Dolo, Amagana; Doumbo, Ogobara; Daou, Modibo; de Jong, Dirk; Joosten, Leo A B; Tissingh, Rudi A; Reubsaet, Frans A G; Sauerwein, Robert; van der Meer, Jos W M; van der Ven, André J A M; Netea, Mihai G

    2009-09-01

    Caspase-12 functions as an antiinflammatory enzyme inhibiting caspase-1 and the NOD2/RIP2 pathways. Due to increased susceptibility to sepsis in individuals with functional caspase-12, an early-stop mutation leading to the loss of caspase-12 has replaced the ancient genotype in Eurasia and a significant proportion of individuals from African populations. In African-Americans, it has been shown that caspase-12 inhibits the pro-inflammatory cytokine production. We assessed whether similar mechanisms are present in African individuals, and whether evolutionary pressures due to plague may have led to the present caspase-12 genotype population frequencies. No difference in cytokine induction through the caspase-1 and/or NOD2/RIP2 pathways was observed in two independent African populations, among individuals with either an intact or absent caspase-12. In addition, stimulations with Yersinia pestis and two other species of Yersinia were preformed to investigate whether caspase-12 modulates the inflammatory reaction induced by Yersinia. We found that caspase-12 did not modulate cytokine production induced by Yersinia spp. Our experiments demonstrate for the first time the involvement of the NOD2/RIP2 pathway for recognition of Yersinia. However, caspase-12 does not modulate innate host defense against Y. pestis and alternative explanations for the geographical distribution of caspase-12 should be sought.

  4. Malarial Pigment Hemozoin and the Innate Inflammatory Response

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    Martin eOlivier

    2014-02-01

    Full Text Available Malaria is a deadly infectious disease caused by the intraerythrocytic protozoan parasite Plasmodium. The four species of Plasmodium known to affect humans all produce an inorganic crystal called hemozoin (HZ during the heme detoxification process. HZ is released from the food vacuole into circulation during erythrocyte lysis, while the released parasites further infect additional naive red blood cells. Once in circulation, HZ is rapidly taken up by circulating monocytes and tissue macrophages, inducing the production of pro-inflammatory mediators, such as interleukin-1β (IL-1β. Over the last few years, it has been reported that HZ, similar to uric acid crystals, asbestos and silica, is able to trigger IL-1β production via the activation of the NOD-like receptor containing pyrin domain 3 (NLRP3 inflammasome complex. Additionally, recent findings have shown that host factors, such as fibrinogen, have the ability to adhere to free HZ and modify its capacity to activate host immune cells. Although much has been discovered regarding NLRP3 inflammasome induction, the mechanism through which this intracellular multimolecular complex is activated remains unclear. In the present review, the most recent discoveries regarding the capacity of HZ to trigger this innate immune complex will be discussed, as well as the impact of HZ on several other inflammatory signalling pathways.

  5. Does CT have an additional diagnostic value over ultrasound in the evaluation of acute inflammatory neck masses in children?

    International Nuclear Information System (INIS)

    Rozovsky, Katya; Hiller, Nurith; Koplewitz, Benjamin Z.; Simanovsky, Natalia

    2010-01-01

    We assessed the additional value of contrast-enhanced CT versus US for evaluation of acute cervical inflammatory masses and choosing treatment strategy. We retrospectively reviewed 210 files of paediatric patients admitted with an acute inflammatory neck mass from 2005 to 2008 (M:F = 108:102, mean age 4.5 years). All patients underwent diagnostic ultrasound and Doppler of the neck; CT was performed in 25 patients within 2-72 h. Clinical and radiological findings were correlated, and imaging impact on patient management was assessed. In the 210 patients, US provided sufficient information in 184 of 185 (99.5%) patients undergoing only US. In one patient with no sonographic evidence of collection, an abscess was drained surgically on the point of fluctuation. Fluid collections were drained in 17 patients based on US findings; inflammatory processes were managed conservatively in 164. CT provided additional information in 4 of 25 patients (16.0%), revealing airways compromise in 2 and collections in 2. US provided sufficient information about the nature, location, and extent of the inflammatory mass in 97.6% of our patients, suggesting it should be the main, and generally single, imaging technique in these patients. CT should be reserved for patients with an aggravating clinical course and suspicion of deep neck infection or airways compromise. (orig.)

  6. Analysis of serum inflammatory mediators identifies unique dynamic networks associated with death and spontaneous survival in pediatric acute liver failure.

    Science.gov (United States)

    Azhar, Nabil; Ziraldo, Cordelia; Barclay, Derek; Rudnick, David A; Squires, Robert H; Vodovotz, Yoram

    2013-01-01

    Tools to predict death or spontaneous survival are necessary to inform liver transplantation (LTx) decisions in pediatric acute liver failure (PALF), but such tools are not available. Recent data suggest that immune/inflammatory dysregulation occurs in the setting of acute liver failure. We hypothesized that specific, dynamic, and measurable patterns of immune/inflammatory dysregulation will correlate with outcomes in PALF. We assayed 26 inflammatory mediators on stored serum samples obtained from a convenience sample of 49 children in the PALF study group (PALFSG) collected within 7 days after enrollment. Outcomes were assessed within 21 days of enrollment consisting of spontaneous survivors, non-survivors, and LTx recipients. Data were subjected to statistical analysis, patient-specific Principal Component Analysis (PCA), and Dynamic Bayesian Network (DBN) inference. Raw inflammatory mediator levels assessed over time did not distinguish among PALF outcomes. However, DBN analysis did reveal distinct interferon-gamma-related networks that distinguished spontaneous survivors from those who died. The network identified in LTx patients pre-transplant was more like that seen in spontaneous survivors than in those who died, a finding supported by PCA. The application of DBN analysis of inflammatory mediators in this small patient sample appears to differentiate survivors from non-survivors in PALF. Patterns associated with LTx pre-transplant were more like those seen in spontaneous survivors than in those who died. DBN-based analyses might lead to a better prediction of outcome in PALF, and could also have more general utility in other complex diseases with an inflammatory etiology.

  7. Analysis of serum inflammatory mediators identifies unique dynamic networks associated with death and spontaneous survival in pediatric acute liver failure.

    Directory of Open Access Journals (Sweden)

    Nabil Azhar

    Full Text Available Tools to predict death or spontaneous survival are necessary to inform liver transplantation (LTx decisions in pediatric acute liver failure (PALF, but such tools are not available. Recent data suggest that immune/inflammatory dysregulation occurs in the setting of acute liver failure. We hypothesized that specific, dynamic, and measurable patterns of immune/inflammatory dysregulation will correlate with outcomes in PALF.We assayed 26 inflammatory mediators on stored serum samples obtained from a convenience sample of 49 children in the PALF study group (PALFSG collected within 7 days after enrollment. Outcomes were assessed within 21 days of enrollment consisting of spontaneous survivors, non-survivors, and LTx recipients. Data were subjected to statistical analysis, patient-specific Principal Component Analysis (PCA, and Dynamic Bayesian Network (DBN inference.Raw inflammatory mediator levels assessed over time did not distinguish among PALF outcomes. However, DBN analysis did reveal distinct interferon-gamma-related networks that distinguished spontaneous survivors from those who died. The network identified in LTx patients pre-transplant was more like that seen in spontaneous survivors than in those who died, a finding supported by PCA.The application of DBN analysis of inflammatory mediators in this small patient sample appears to differentiate survivors from non-survivors in PALF. Patterns associated with LTx pre-transplant were more like those seen in spontaneous survivors than in those who died. DBN-based analyses might lead to a better prediction of outcome in PALF, and could also have more general utility in other complex diseases with an inflammatory etiology.

  8. Neonatal overfeeding attenuates acute central pro-inflammatory effects of short-term high fat diet

    Directory of Open Access Journals (Sweden)

    Guohui eCai

    2015-01-01

    Full Text Available Neonatal obesity predisposes individuals to obesity throughout life. In rats, neonatal overfeeding also leads to early accelerated weight gain that persists into adulthood. The phenotype is associated with dysfunction in a number of systems including paraventricular nucleus of the hypothalamus (PVN responses to psychological and immune stressors. However, in many cases weight gain in neonatally overfed rats stabilizes in early adulthood so the animal does not become more obese as it ages. Here we examined if neonatal overfeeding by suckling rats in small litters predisposes them to exacerbated metabolic and central inflammatory disturbances if they are also given a high fat diet in later life. In adulthood we gave the rats normal chow, 3 days, or 3 weeks high fat diet (45% kcal from fat and measured peripheral indices of metabolic disturbance. We also investigated hypothalamic microglial changes, as an index of central inflammation, as well as PVN responses to lipopolysaccharide (LPS. Surprisingly, neonatal overfeeding did not predispose rats to the metabolic effects of a high fat diet. Weight changes and glucose metabolism were unaffected by the early life experience. However, short term (3 day high fat diet was associated with more microglia in the hypothalamus and a markedly exacerbated PVN response to LPS in control rats; effects not seen in the neonatally overfed. Our findings indicate neonatally overfed animals are not more susceptible to the adverse metabolic effects of a short-term high fat diet but may be less able to respond to the central effects.

  9. Acute phase response to surgery of varying intensity in horses

    DEFF Research Database (Denmark)

    Jacobsen, Stine; Nielsen, Jon Vedding; Kjelgaard-Hansen, Mads

    2009-01-01

    OBJECTIVE: To evaluate the postoperative inflammatory response of horses to elective surgery of varying intensity. STUDY DESIGN: Prospective longitudinal study. ANIMALS: Horses referred to 2 hospitals for either arthroscopic removal of a unilateral osteochondritic lesion in the tibiotarsal joint...... (WBC) counts and concentrations of serum amyloid A (SAA), fibrinogen, and iron were assessed in blood samples obtained before, and 1-3, 5, 7, 9, and 11 days after surgery. Differences in levels of the inflammatory markers between the 3 surgical groups were analyzed using repeated measures ANOVA...

  10. Symposium review: Oxylipids and the regulation of bovine mammary inflammatory responses.

    Science.gov (United States)

    Sordillo, Lorraine M

    2018-01-31

    Inflammation is a critical aspect of the innate immune system that can determine the outcome of several economically important diseases of dairy cattle such as mastitis. The purpose of the inflammatory response is to eliminate the source of tissue injury and then return tissues to normal function. Aggressive or uncontrolled inflammatory responses, however, can damage host tissues and contribute significantly to the pathophysiology associated with mastitis. A precarious balance between pro-inflammatory and pro-resolving mechanisms is needed to ensure optimal pathogen clearance and a prompt return to immune homeostasis. Therefore, inflammatory responses must be tightly regulated to avoid bystander damage to the milk-synthesizing tissues of the mammary gland. Oxylipids are potent lipid mediators that can regulate all aspects of the inflammatory response. The biosynthetic profiles of oxylipids are dependent on both the availability of diverse polyunsaturated fatty acids substrates and their subsequent metabolism through various oxidizing pathways. Changes in lipid metabolism in dairy cows around parturition can profoundly change the composition and concentration of oxylipids in the mammary gland that may be responsible for dysfunctional inflammatory responses during this time. This review will provide a brief overview of the bovine inflammatory response and the role that oxylipids play in contributing to the onset and resolution of inflammation especially as it pertains to mastitis. Factors associated with periparturient cows that can contribute to dysfunctional regulation of inflammation as a function of altered oxylipid biosynthesis and metabolism also will be described. Understanding the role that oxylipids may play in the development of mastitis is key to developing novel prevention and control programs for the dairy industry. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  11. Reduced tonicity stimulates an inflammatory response in nucleus pulposus tissue that can be limited by a COX-2-specific inhibitor.

    NARCIS (Netherlands)

    van Dijk, Bart; Potier, Esther; van Dijk, Maarten; Langelaan, Marloes; Papen-Botterhuis, Nicole; Ito, K

    2015-01-01

    In intervertebral disc herniation with nucleus pulposus (NP) extrusion, the elicited inflammatory response is considered a key pain mechanism. However, inflammatory cytokines are reported in extruded herniated tissue, even before monocyte infiltration, suggesting that the tissue itself initiates the

  12. Reduced Tonicity Stimulates an Inflammatory Response in Nucleus Pulposus Tissue That Can Be Limited by a COX-2-Specific Inhibitor

    NARCIS (Netherlands)

    Dijk, B. van; Potier, E.; Dijk, M. van; Langelaan, M.; Papen-Botterhuis, N.E.; Ito, K.

    2015-01-01

    In intervertebral disc herniation with nucleus pulposus (NP) extrusion, the elicited inflammatory response is considered a key pain mechanism. However, inflammatory cytokines are reported in extruded herniated tissue, even before monocyte infiltration, suggesting that the tissue itself initiates the

  13. AGEs secreted by bacteria are involved in the inflammatory response.

    Directory of Open Access Journals (Sweden)

    Ifat Cohen-Or

    Full Text Available Advanced Glycated End Products (AGEs are formed by non-enzymatic protein glycation and are implicated in several physiological aspects including cell aging and diseases. Recent data indicate that bacteria--although short lived--produce, metabolize and accumulate AGEs. Here we show that Escherichia coli cells secret AGEs by the energy-dependent efflux pump systems. Moreover, we show that in the presence of these AGEs there is an upshift of pro-inflammatory cytokins by mammalian cells. Thus, we propose that secretion of AGEs by bacteria is a novel avenue of bacterial-induced inflammation which is potentially important in the pathophysiology of bacterial infections. Moreover, the sensing of AGEs by the host cells may constitute a warning system for the presence of bacteria.

  14. p120-catenin mediates inflammatory responses in the skin

    DEFF Research Database (Denmark)

    Perez-Moreno, Mirna; Davis, Michael A; Wong, Ellen

    2006-01-01

    Although p120-catenin regulates adherens junction (AJ) stability in cultured cells, genetic studies in lower eukaryotes have not revealed a role for this protein in vivo. Using conditional targeting in mice, we show that p120 null neonatal epidermis exhibits reduced intercellular AJ components...... but no overt disruption in barrier function or intercellular adhesion. As the mice age, however, they display epidermal hyperplasia and chronic inflammation, typified by hair degeneration and loss of body fat. Using skin engraftments and anti-inflammatory drugs, we show that these features are not attributable...... to reductions in junctional cadherins and catenins, but rather NFkB activation. Both in vivo and in vitro, p120 null epidermal cells activate nuclear NFkB, triggering a cascade of proinflammatory NFkB targets. Although the underlying mechanism is likely complex, we show that p120 affects NFkB activation...

  15. Sirt2 suppresses inflammatory responses in collagen-induced arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Jiangtao [Department of Orthopaedics, Qilu Hospital, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China); Department of Orthopaedics, Yantaishan Hospital, 91 Jiefang Road, Yantai, Shandong 264001 (China); Sun, Bing; Jiang, Chuanqiang; Hong, Huanyu [Department of Orthopaedics, Yantaishan Hospital, 91 Jiefang Road, Yantai, Shandong 264001 (China); Zheng, Yanping, E-mail: yanpingzheng@yahoo.com [Department of Orthopaedics, Qilu Hospital, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China)

    2013-11-29

    Highlights: •Sirt2 expression decreases in collagen-induced arthritis (CIA). •Sirt2 knockout aggravates severity of arthritis in mice with CIA. •Sirt2 knockout increases levels of pro-inflammatory factors in the serum. •Sirt2 deacetylates p65 and inhibits pro-inflammatory factors expression. •Sirt2 rescue abates severity of arthritis in mice with CIA. -- Abstract: Arthritis is a common autoimmune disease that is associated with progressive disability, systemic complications and early death. However, the underling mechanisms of arthritis are still unclear. Sirtuins are a NAD{sup +}-dependent class III deacetylase family, and regulate cellular stress, inflammation, genomic stability, carcinogenesis, and energy metabolism. Among the sirtuin family members, Sirt1 and Sirt6 are critically involved in the development of arthritis. It remains unknown whether other sirtuin family members participate in arthritis. Here in this study, we demonstrate that Sirt2 inhibits collagen-induced arthritis (CIA) using in vivo and in vitro evidence. The protein and mRNA levels of Sirt2 significantly decreased in joint tissues of mice with CIA. When immunized with collagen, Sirt2-KO mice showed aggravated severity of arthritis based on clinical scores, hind paw thickness, and radiological and molecular findings. Mechanically, Sirt2 deacetylated p65 subunit of nuclear factor-kappa B (NF-κB) at lysine 310, resulting in reduced expression of NF-κB-dependent genes, including interleukin 1β (IL-1β), IL-6, monocyte chemoattractant protein 1(MCP-1), RANTES, matrix metalloproteinase 9 (MMP-9) and MMP-13. Importantly, our rescue experiment showed that Sirt2 re-expression abated the severity of arthritis in Sirt2-KO mice. Those findings strongly indicate Sirt2 as a considerably inhibitor of the development of arthritis.

  16. Weight cycling enhances adipose tissue inflammatory responses in male mice.

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    Sandra Barbosa-da-Silva

    Full Text Available BACKGROUND: Obesity is associated with low-grade chronic inflammation attributed to dysregulated production, release of cytokines and adipokines and to dysregulated glucose-insulin homeostasis and dyslipidemia. Nutritional interventions such as dieting are often accompanied by repeated bouts of weight loss and regain, a phenomenon known as weight cycling (WC. METHODS: In this work we studied the effects of WC on the feed efficiency, blood lipids, carbohydrate metabolism, adiposity and inflammatory markers in C57BL/6 male mice that WC two or three consecutive times by alternation of a high-fat (HF diet with standard chow (SC. RESULTS: The body mass (BM grew up in each cycle of HF feeding, and decreased after each cycle of SC feeding. The alterations observed in the animals feeding HF diet in the oral glucose tolerance test, in blood lipids, and in serum and adipose tissue expression of adipokines were not recuperated after WC. Moreover, the longer the HF feeding was (two, four and six months, more severe the adiposity was. After three consecutive WC, less marked was the BM reduction during SC feeding, while more severe was the BM increase during HF feeding. CONCLUSION: In conclusion, the results of the present study showed that both the HF diet and WC are relevant to BM evolution and fat pad remodeling in mice, with repercussion in blood lipids, homeostasis of glucose-insulin and adipokine levels. The simple reduction of the BM during a WC is not able to recover the high levels of adipokines in the serum and adipose tissue as well as the pro-inflammatory cytokines enhanced during a cycle of HF diet. These findings are significant because a milieu with altered adipokines in association with WC potentially aggravates the chronic inflammation attributed to dysregulated production and release of adipokines in mice.

  17. Extracellular histones play an inflammatory role in acid aspiration-induced acute respiratory distress syndrome.

    Science.gov (United States)

    Zhang, Yanlin; Wen, Zongmei; Guan, Li; Jiang, Ping; Gu, Tao; Zhao, Jinyuan; Lv, Xin; Wen, Tao

    2015-01-01

    Systemic inflammation is a key feature in acid aspiration-induced acute respiratory distress syndrome (ARDS), but the factors that trigger inflammation are unclear. The authors hypothesize that extracellular histones, a newly identified inflammatory mediator, play important roles in the pathogenesis of ARDS. The authors used a hydrochloric acid aspiration-induced ARDS model to investigate whether extracellular histones are pathogenic and whether targeting histones are protective. Exogenous histones and antihistone antibody were administered to mice. Heparin can bind to histones, so the authors studied whether heparin could protect from ARDS using cell and mouse models. Furthermore, the authors analyzed whether extracellular histones are clinically involved in ARDS patients caused by gastric aspiration. Extracellular histones in bronchoalveolar lavage fluid of acid-treated mice were significantly higher (1.832 ± 0.698) at 3 h after injury than in sham-treated group (0.63 ± 0.153; P = 0.0252, n = 5 per group). Elevated histones may originate from damaged lung cells and neutrophil infiltration. Exogenous histones aggravated lung injury, whereas antihistone antibody markedly attenuated the intensity of ARDS. Notably, heparin provided a similar protective effect against ARDS. Analysis of plasma from ARDS patients (n = 21) showed elevated histones were significantly correlated with the degree of ARDS and were higher in nonsurvivors (2.723 ± 0.2933, n = 7) than in survivors (1.725 ± 0.1787, P = 0.006, n = 14). Extracellular histones may play a contributory role toward ARDS by promoting tissue damage and systemic inflammation and may become a novel marker reflecting disease activity. Targeting histones by neutralizing antibody or heparin shows potent protective effects, suggesting a potentially therapeutic strategy.

  18. Bee Venom Decreases LPS-Induced Inflammatory Responses in Bovine Mammary Epithelial Cells.

    Science.gov (United States)

    Jeong, Chang Hee; Cheng, Wei Nee; Bae, Hyojin; Lee, Kyung Woo; Han, Sang Mi; Petriello, Michael C; Lee, Hong Gu; Seo, Han Geuk; Han, Sung Gu

    2017-10-28

    The world dairy industry has long been challenged by bovine mastitis, an inflammatory disease, which causes economic loss due to decreased milk production and quality. Attempts have been made to prevent or treat this disease with multiple approaches, primarily through increased abuse of antibiotics, but effective natural solutions remain elusive. Bee venom (BV) contains a variety of peptides ( e.g. , melittin) and shows multiple bioactivities, including prevention of inflammation. Thus, in the current study, it was hypothesized that BV can reduce inflammation in bovine mammary epithelial cells (MAC-T). To examine the hypothesis, cells were treated with LPS (1 μg/ml) to induce an inflammatory response and the anti-inflammatory effects of BV (2.5 and 5 μg/ml) were investigated. The cellular mechanisms of BV against LPS-induced inflammation were also investigated. Results showed that BV can attenuate expression of an inflammatory protein, COX2, and pro-inflammatory cytokines such as IL-6 and TNF-α. Activation of NF-κB, an inflammatory transcription factor, was significantly downregulated by BV in cells treated with LPS, through dephosphorylation of ERK1/2. Moreover, pretreatment of cells with BV attenuated LPS-induced production of intracellular reactive oxygen species ( e.g. , superoxide anion). These results support our hypothesis that BV can decrease LPS-induced inflammatory responses in bovine mammary epithelial cells through inhibition of oxidative stress, NF-κB, ERK1/2, and COX-2 signaling.

  19. Acute and Post-Exercise Physiological Responses to High-Intensity Interval Training in Endurance and Sprint Athletes

    OpenAIRE

    Cipryan, Lukas; Tschakert, Gerhard; Hofmann, Peter

    2017-01-01

    The purpose of the presented study was to compare acute and post-exercise differences in cardiorespiratory, metabolic, cardiac autonomic, inflammatory and muscle damage responses to high-intensity interval exercise (HIIT) between endurance and sprint athletes. The study group consisted of sixteen highly-trained males (age 22.1 �� 2.5 years) participating in endurance (n = 8) or sprint (n = 8) sporting events. All the participants underwent three exercise sessions: short HIIT (work interval du...

  20. Acute and Post-Exercise Physiological Responses to High-Intensity Interval Training in Endurance and Sprint Athletes

    OpenAIRE

    Lukas Cipryan, Gerhard Tschakert, Peter Hofmann

    2017-01-01

    The purpose of the presented study was to compare acute and post-exercise differences in cardiorespiratory, metabolic, cardiac autonomic, inflammatory and muscle damage responses to high-intensity interval exercise (HIIT) between endurance and sprint athletes. The study group consisted of sixteen highly-trained males (age 22.1 ± 2.5 years) participating in endurance (n = 8) or sprint (n = 8) sporting events. All the participants underwent three exercise sessions: short HIIT (work interval dur...

  1. Dissemination of Orientia tsutsugamushi and inflammatory responses in a murine model of scrub typhus.

    Directory of Open Access Journals (Sweden)

    Christian A Keller

    2014-08-01

    Full Text Available Central aspects in the pathogenesis of scrub typhus, an infection caused by Orientia (O. tsutsugamushi, have remained obscure. Its organ and cellular tropism are poorly understood. The purpose of this study was to analyze the kinetics of bacterial dissemination and associated inflammatory responses in infected tissues in an experimental scrub typhus mouse model, following infection with the human pathogenic strain Karp. We provide a thorough analysis of O. tsutsugamushi infection in inbred Balb/c mice using footpad inoculation, which is close to the natural way of infection. By a novel, highly sensitive qPCR targeting the multi copy traD genes, we quantitatively monitored the spread of O. tsutsugamushi Karp from the skin inoculation site via the regional lymph node to the internal target organs. The highest bacterial loads were measured in the lung. Using confocal imaging, we also detected O. tsutsugamushi at the single cell level in the lung and found a predominant macrophage rather than endothelial localization. Immunohistochemical analysis of infiltrates in lung and brain revealed differently composed lesions with specific localizations: iNOS-expressing macrophages were frequent in infiltrative parenchymal noduli, but uncommon in perivascular lesions within these organs. Quantitative analysis of the macrophage response by immunohistochemistry in liver, heart, lung and brain demonstrated an early onset of macrophage activation in the liver. Serum levels of interferon (IFN-γ were increased during the acute infection, and we showed that IFN-γ contributed to iNOS-dependent bacterial growth control. Our data show that upon inoculation to the skin, O. tsutsugamushi spreads systemically to a large number of organs and gives rise to organ-specific inflammation patterns. The findings suggest an essential role for the lung in the pathogenesis of scrub typhus. The model will allow detailed studies on host-pathogen interaction and provide further

  2. Acute sleep fragmentation does not alter pro-inflammatory cytokine gene expression in brain or peripheral tissues of leptin-deficient mice

    Directory of Open Access Journals (Sweden)

    Jennifer E. Dumaine

    2018-02-01

    Full Text Available Obesity and sleep fragmentation (SF are often co-occurring pro-inflammatory conditions in patients with obstructive sleep apnea. Leptin is a peptide hormone produced by adipocytes that has anorexigenic effects upon appetite while regulating immunity. The role of leptin in mediating inflammatory responses to SF is incompletely understood. Male C57BL/6j (lean and ob/ob mice (leptin-deficient mice exhibiting obese phenotype were subjected to SF or control conditions for 24 h using an automated SF chamber. Trunk blood and tissue samples from the periphery (liver, spleen, fat, and heart and brain (hypothalamus, prefrontal cortex, and hippocampus were collected. Quantitative PCR was used to determine relative cytokine gene expression of pro-inflammatory (IL-1β, TNF-α and anti-inflammatory (TGF-β1 cytokines. Enzyme-linked immunosorbent assay (ELISA was used to determine serum corticosterone concentration. Ob/ob mice exhibited elevated cytokine gene expression in liver (TNF-α, TGF-β1, heart (TGF-β1, fat (TNF-α, and brain (hippocampus, hypothalamus, prefrontal cortex: IL-1β, TNF-α compared with wild-type mice. Conversely, leptin deficiency decreased pro-inflammatory cytokine gene expression in heart (IL-1β, TNF-α. SF significantly increased IL-1β and TNF-α gene expression in fat and TGF-β1 expression in spleen relative to controls, but only in wild-type mice. SF increased basal serum corticosterone regardless of genotype. Taken together, these findings suggest that leptin deficiency affects cytokine gene expression differently in the brain compared to peripheral tissues with minimal interaction from acute SF.

  3. An intense and short-lasting burst of neutrophil activation differentiates early acute myocardial infarction from systemic inflammatory syndromes.

    Directory of Open Access Journals (Sweden)

    Norma Maugeri

    Full Text Available BACKGROUND: Neutrophils are involved in thrombus formation. We investigated whether specific features of neutrophil activation characterize patients with acute coronary syndromes (ACS compared to stable angina and to systemic inflammatory diseases. METHODS AND FINDINGS: The myeloperoxidase (MPO content of circulating neutrophils was determined by flow cytometry in 330 subjects: 69 consecutive patients with acute coronary syndromes (ACS, 69 with chronic stable angina (CSA, 50 with inflammation due to either non-infectious (acute bone fracture, infectious (sepsis or autoimmune diseases (small and large vessel systemic vasculitis, rheumatoid arthritis. Four patients have also been studied before and after sterile acute injury of the myocardium (septal alcoholization. One hundred thirty-eight healthy donors were studied in parallel. Neutrophils with normal MPO content were 96% in controls, >92% in patients undergoing septal alcoholization, 91% in CSA patients, but only 35 and 30% in unstable angina and AMI (STEMI and NSTEMI patients, compared to 80%, 75% and 2% of patients with giant cell arteritis, acute bone fracture and severe sepsis. In addition, in 32/33 STEMI and 9/21 NSTEMI patients respectively, 20% and 12% of neutrophils had complete MPO depletion during the first 4 hours after the onset of symptoms, a feature not observed in any other group of patients. MPO depletion was associated with platelet activation, indicated by P-selectin expression, activation and transactivation of leukocyte β2-integrins and formation of platelet neutrophil and -monocyte aggregates. The injection of activated platelets in mice produced transient, P-selectin dependent, complete MPO depletion in about 50% of neutrophils. CONCLUSIONS: ACS are characterized by intense neutrophil activation, like other systemic inflammatory syndromes. In the very early phase of acute myocardial infarction only a subpopulation of neutrophils is massively activated, possibly via

  4. African Trypanosomes Undermine Humoral Responses and Vaccine Development: Link with Inflammatory Responses?

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    Benoit Stijlemans

    2017-05-01

    Full Text Available African trypanosomosis is a debilitating disease of great medical and socioeconomical importance. It is caused by strictly extracellular protozoan parasites capable of infecting all vertebrate classes including human, livestock, and game animals. To survive within their mammalian host, trypanosomes have evolved efficient immune escape mechanisms and manipulate the entire host immune response, including the humoral response. This report provides an overview of how trypanosomes initially trigger and subsequently undermine the development of an effective host antibody response. Indeed, results available to date obtained in both natural and experimental infection models show that trypanosomes impair homeostatic B-cell lymphopoiesis, B-cell maturation and survival and B-cell memory development. Data on B-cell dysfunctioning in correlation with parasite virulence and trypanosome-mediated inflammation will be discussed, as well as the impact of trypanosomosis on heterologous vaccine efficacy and diagnosis. Therefore, new strategies aiming at enhancing vaccination efficacy could benefit from a combination of (i early parasite diagnosis, (ii anti-trypanosome (drugs treatment, and (iii anti-inflammatory treatment that collectively might allow B-cell recovery and improve vaccination.

  5. Nitro-oleic acid inhibits vascular endothelial inflammatory responses and the endothelial-mesenchymal transition.

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    Ambrozova, Gabriela; Fidlerova, Tana; Verescakova, Hana; Koudelka, Adolf; Rudolph, Tanja K; Woodcock, Steven R; Freeman, Bruce A; Kubala, Lukas; Pekarova, Michaela

    2016-11-01

    Inflammatory-mediated pathological processes in the endothelium arise as a consequence of the dysregulation of vascular homeostasis. Of particular importance are mediators produced by stimulated monocytes/macrophages inducing activation of endothelial cells (ECs). This is manifested by excessive soluble pro-inflammatory mediator production and cell surface adhesion molecule expression. Nitro-fatty acids are endogenous products of metabolic and inflammatory reactions that display immuno-regulatory potential and may represent a novel therapeutic strategy to treat inflammatory diseases. The purpose of our study was to characterize the effects of nitro-oleic acid (OA-NO2) on inflammatory responses and the endothelial-mesenchymal transition (EndMT) in ECs that is a consequence of the altered healing phase of the immune response. The effect of OA-NO2 on inflammatory responses and EndMT was determined in murine macrophages and murine and human ECs using Western blotting, ELISA, immunostaining, and functional assays. OA-NO2 limited the activation of macrophages and ECs by reducing pro-inflammatory cytokine production and adhesion molecule expression through its modulation of STAT, MAPK and NF-κB-regulated signaling. OA-NO2 also decreased transforming growth factor-β-stimulated EndMT and pro-fibrotic phenotype of ECs. These effects are related to the downregulation of Smad2/3. The study shows the pleiotropic effect of OA-NO2 on regulating EC-macrophage interactions during the immune response and suggests a role for OA-NO2 in the regulation of vascular endothelial immune and fibrotic responses arising during chronic inflammation. These findings propose the OA-NO2 may be useful as a novel therapeutic agent for treatment of cardiovascular disorders associated with dysregulation of the endothelial immune response. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Melatonin modulates the fetal cardiovascular defense response to acute hypoxia.

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    Thakor, Avnesh S; Allison, Beth J; Niu, Youguo; Botting, Kimberley J; Serón-Ferré, Maria; Herrera, Emilio A; Giussani, Dino A

    2015-08-01

    Experimental studies in animal models supporting protective effects on the fetus of melatonin in adverse pregnancy have prompted clinical trials in human pregnancy complicated by fetal growth restriction. However, the effects of melatonin on the fetal defense to acute hypoxia, such as that which may occur during labor, remain unknown. This translational study tested the hypothesis, in vivo, that melatonin modulates the fetal cardiometabolic defense responses to acute hypoxia in chronically instrumented late gestation fetal sheep via alterations in fetal nitric oxide (NO) bioavailability. Under anesthesia, 6 fetal sheep at 0.85 gestation were instrumented with vascular catheters and a Transonic flow probe around a femoral artery. Five days later, fetuses were exposed to acute hypoxia with or without melatonin treatment. Fetal blood was taken to determine blood gas and metabolic status and plasma catecholamine concentrations. Hypoxia during melatonin treatment was repeated during in vivo NO blockade with the NO clamp. This technique permits blockade of de novo synthesis of NO while compensating for the tonic production of the gas, thereby maintaining basal cardiovascular function. Melatonin suppressed the redistribution of blood flow away from peripheral circulations and the glycemic and plasma catecholamine responses to acute hypoxia. These are important components of the fetal brain sparing response to acute hypoxia. The effects of melatonin involved NO-dependent mechanisms as the responses were reverted by fetal treatment with the NO clamp. Melatonin modulates the in vivo fetal cardiometabolic responses to acute hypoxia by increasing NO bioavailability. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. High serum soluble tumor necrosis factor receptor 1 predicts poor treatment response in acute-stage schizophrenia.

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    Nishimon, Shohei; Ohnuma, Tohru; Takebayashi, Yuto; Katsuta, Narimasa; Takeda, Mayu; Nakamura, Toru; Sannohe, Takahiro; Higashiyama, Ryoko; Kimoto, Ayako; Shibata, Nobuto; Gohda, Tomohito; Suzuki, Yusuke; Yamagishi, Sho-Ichi; Tomino, Yasuhiko; Arai, Heii

    2017-06-02

    Inflammation may be involved in the pathophysiology of schizophrenia. However, few cross-sectional or longitudinal studies have examined changes in biomarker expression to evaluate diagnostic and prognostic efficacy in acute-stage schizophrenia. We compared serum inflammatory biomarker concentrations in 87 patients with acute-stage schizophrenia on admission to 105 age-, sex-, and body mass index (BMI)-matched healthy controls. The measured biomarkers were soluble tumor necrosis factor receptor 1 (sTNFR1) and adiponectin, which are associated with inflammatory responses, and pigment epithelium-derived factor (PEDF), which has anti-inflammatory properties. We then investigated biomarker concentrations and associations with clinical factors in 213 patients (including 42 medication-free patients) and 110 unmatched healthy controls to model conditions typical of clinical practice. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale and Global Assessment of Function. In 121 patients, biomarker levels and clinical status were evaluated at both admission and discharge. Serum sTNFR1 was significantly higher in patients with acute-stage schizophrenia compared to matched controls while no significant group differences were observed for the other markers. Serum sTNFR1 was also significantly higher in the 213 patients compared to unmatched controls. The 42 unmedicated patients had significantly lower PEDF levels compared to controls. Between admission and discharge, sTNFR1 levels decreased significantly; however, biomarker changes did not correlate with clinical symptoms. The discriminant accuracy of sTNFR1 was 93.2% between controls and patients, showing no symptom improvement during care. Inflammation and a low-level anti-inflammatory state may be involved in both schizophrenia pathogenesis and acute-stage onset. High serum sTNFR1 in the acute stage could be a useful prognostic biomarker for treatment response in clinical practice. Copyright © 2017

  8. Correlation of serum Dickkopf-1 content with bone destruction, inflammatory response and oxidation reaction in patients with gouty arthritis

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    Yu-Mei He

    2017-09-01

    Full Text Available Objective: To study the correlation of serum Dickkopf-1 (DKK-1 content with bone destruction, inflammatory response and oxidation reaction in patients with gouty arthritis. Methods: A total of 40 patients with acute gouty arthritis who were treated in our hospital between 2013 and 2016 were selected as the group A of the study, 56 patients with asymptomatic hyperuricemia who were treated in our hospital during the same period were selected as the group B of the study, and 60 healthy volunteers who received physical examination in our hospital during the same period were selected as the control group of the study. The serum was collected to detect the contents of DKK-1, bone destruction indexes, inflammatory response indexes and oxidation reaction indexes. Results: Serum DKK-1, TRACP5b, RANKL, β-CTX, PGE2, sICAM-1, sVCAM-1, sCD14, MDA, 8-OHdG and 3-NT levels of group A and group B were significantly higher than those of control group while SOD and GSH-Px levels were significantly lower than those of control group; serum DKK-1, TRACP5b, RANKL, β-CTX, PGE2, sICAM-1, sVCAM-1, sCD14, MDA, 8-OHdG and 3-NT levels of group A were significantly higher than those of group B while SOD and GSH-Px levels were significantly lower than those of group B; serum DKK-1 level was positively correlated with TRACP5b, RANKL, β-CTX, PGE2, sICAM-1, sVCAM-1, sCD14, MDA, 8-OHdG and 3-NT levels, and negatively correlated with SOD and GSH-Px levels. Conclusion: Abnormally elevated DKK-1 in patients with gouty arthritis can induce articular bone destruction as well as inflammatory response and oxidative stress response activation.

  9. Multicomponent Moraxella catarrhalis outer membrane vesicles induce an inflammatory response and are internalized by human epithelial cells.

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    Schaar, Viveka; de Vries, Stefan P W; Perez Vidakovics, Maria Laura A; Bootsma, Hester J; Larsson, Lennart; Hermans, Peter W M; Bjartell, Anders; Mörgelin, Matthias; Riesbeck, Kristian

    2011-03-01

    Moraxella catarrhalis is an emerging human respiratory pathogen in patients with chronic obstructive pulmonary disease (COPD) and in children with acute otitis media. The specific secretion machinery known as outer membrane vesicles (OMVs) is a mechanism by which Gram-negative pathogens interact with host cells during infection. We identified 57 proteins in M. catarrhalis OMVs using a proteomics approach combining two-dimensional SDS-PAGE and MALDI-TOF mass spectrometry analysis. The OMVs contained known surface proteins such as ubiquitous surface proteins (Usp) A1/A2, and Moraxella IgD-binding protein (MID). Most of the proteins are adhesins/virulence factors triggering the immune response, but also aid bacteria to evade the host defence. FITC-stained OMVs bound to lipid raft domains in alveolar epithelial cells and were internalized after interaction with Toll-like receptor 2 (TLR2), suggesting a delivery to the host tissue of a large and complex group of OMV-attributed proteins. Interestingly, OMVs modulated the pro-inflammatory response in epithelial cells, and UspA1-bearing OMVs were found to specifically downregulate the reaction. When mice were exposed to OMVs, a pulmonary inflammation was clearly seen. Our findings indicate that Moraxella OMVs are highly biologically active, transport main bacterial virulence factors and may modulate the epithelial pro-inflammatory response. © 2010 Blackwell Publishing Ltd.

  10. Inflammatory Response to Lipopolysaccharide on the Ocular Surface in a Murine Dry Eye Model.

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    Simmons, Ken T; Xiao, Yangyan; Pflugfelder, Stephen C; de Paiva, Cintia S

    2016-05-01

    Toll-like receptor 4 (TLR4) alerts cells to the presence of bacteria by initiating an inflammatory response. We hypothesize that disruption of the ocular surface barrier in dry eye enhances TLR4 signaling. This study determined whether dry eye enhances expression of inflammatory mediators in response to topically applied TLR4 ligand. A single dose of lipopolysaccharide (LPS) or vehicle (endotoxin-free water) was applied to the cornea of nonstressed (NS) mice or mice subjected to 5 days of desiccating stress (DS). After 4 hours, corneal epithelium and conjunctiva were extracted to analyze expression of inflammatory mediators via PCR. Protein expression was confirmed by immunobead assay and immunostaining. Topically applied LPS increased expression of inflammatory mediators IL-1β, CXCL10, IL-12a, and IFN-γ in the conjunctiva, and IL-1β and CXCL10 in the cornea of NS mice compared to that in untreated controls. LPS in DS mice produced 3-fold increased expression of IL-1β in cornea and 2-fold increased expression in IL-12a in conjunctiva compared to that in LPS-treated control mice. LPS increased expression of inflammatory cytokines on the ocular surface. This expression was further increased in dry eye, which suggests that epithelial barrier disruption enhances exposure of LPS to TLR4+ cells and that the inflammatory response to endotoxin-producing commensal or pathogenic bacteria may be more severe in dry eye disease.

  11. 4T1 Murine Mammary Carcinoma Cells Enhance Macrophage-Mediated Innate Inflammatory Responses.

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    Laurence Madera

    Full Text Available Tumor progression and the immune response are intricately linked. While it is known that cancers alter macrophage inflammatory responses to promote tumor progression, little is known regarding how cancers affect macrophage-dependent innate host defense. In this study, murine bone-marrow-derived macrophages (BMDM were exposed to murine carcinoma-conditioned media prior to assessment of the macrophage inflammatory response. BMDMs exposed to 4T1 mammary carcinoma-conditioned medium demonstrated enhanced production of pro-inflammatory cytokines tumor necrosis factor α, interleukin-6, and CCL2 in response to lipopolysaccharide (LPS while production of interleukin-10 remained unchanged. The increased LPS-induced production of pro-inflammatory cytokines was transient and correlated with enhanced cytokine production in response to other Toll-like receptor agonists, including peptidoglycan and flagellin. In addition, 4T1-conditioned BMDMs exhibited strengthened LPS-induced nitric oxide production and enhanced phagocytosis of Escherichia coli. 4T1-mediated augmentation of macrophage responses to LPS was partially dependent on the NFκB pathway, macrophage-colony stimulating factor, and actin polymerization, as well as the presence of 4T1-secreted extracellular vesicles. Furthermore, peritoneal macrophages obtained from 4T1 tumor-bearing mice displayed enhanced pro-inflammatory cytokine production in response to LPS. These results suggest that uptake of 4T1-secreted factors and actin-mediated ingestion of 4T1-secreted exosomes by macrophages cause a transient enhancement of innate inflammatory responses. Mammary carcinoma-mediated regulation of innate immunity may have significant implications for our understanding of host defense and cancer progression.

  12. G protein coupled receptors signaling pathways implicate in inflammatory and immune response of rheumatoid arthritis.

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    Shu, Jinling; Zhang, Feng; Zhang, Lingling; Wei, Wei

    2017-05-01

    G protein-coupled receptors (GPCRs) are transmembrane receptor proteins, which allow the transfer of signals across the membrane. Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis and accompanied with inflammatory and abnormal immune response. GPCRs signaling pathways play a significant role in inflammatory and immune response processes including RA. In this review, we have focused on the advances in GPCRs signaling pathway implicating the inflammatory and immune response of RA. The signaling pathways of GPCRs-adenylyl cyclase (AC)-cyclic adenosine 3', 5'-monophosphate (cAMP) include β 2 adrenergic receptors (β 2 -ARs)-AC-cAMP signaling pathways, E-prostanoid2/4 (EP2/4)-AC-cAMP signaling pathways and so on. Regulatory proteins, such as G protein-coupled receptor kinases (GRKs) and β-arrestins, play important modulatory roles in GPCRs signaling pathway. GPCRs signaling pathway and regulatory proteins implicate the pathogenesis process of inflammatory and immune response. GPCRs-AC-cAMP signal pathways involve in the inflammatory and immune response of RA. Different signaling pathways are mediated by different receptors, such as β 2 -AR, PGE2 receptor, chemokines receptor, and adenosine receptor. GRKs and β-arrestins are crucial proteins in the regulation of GPCRs signaling pathways. The potential therapeutic targets as well as strategies to modulate GPCRs signaling pathway are new development trends.

  13. Regulation of human life histories: the role of the inflammatory host response.

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    Van Bodegom, David; May, Linda; Meij, Hans J; Westendorp, Rudi G J

    2007-04-01

    Most species with a long life span have few offspring while species with a short life span have many offspring. This evolutionary trade-off between fertility and body maintenance, based on the theory of r/K-selection, is a central theme in the theory of life history regulation. This trade-off is not only found between various species but also between individuals within one species. There is accumulating evidence for this trade-off in humans. We hypothesize that the innate immune system is a critical factor skewing an individual into the direction of either a high fertility or better maintenance strategy. As over thousands of years human survival has been highly dependent on resistance to infectious diseases, genetic adaptations resulting in inflammatory responses were favored. An inflammatory host response is critical to fight infection necessary to survive up to reproductive age. An inflammatory host response is also negatively associated with fertility and can explain for the trade-off between fertility and body maintenance. After human reproductive age, these inflammatory responses contribute also to development of chronic degenerative diseases. These will especially become apparent in affluent societies where the majority of individuals reach old age. Identifying the inflammatory host response as a critical factor both in the regulation of human life histories and in the occurrence of chronic diseases at old age implies means for intervention allowing individuals to live healthier for longer.

  14. Mountain Cycling Ultramarathon Effects on Inflammatory and Hemoglobin Responses.

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    Alonso, Isanete; Matos, Andreia; Ribeiro, Ricardo; Gil, Ângela; Cardoso, Carlos; Sardinha, Luís B; Bicho, Manuel

    2018-02-01

    This study aimed to analyze the cumulative physiological burden of repetitive, strenuous exercise held during mountain cycling ultramarathon on regulatory mechanisms of hemoglobin degradation. Fifty-five nonprofessional athletes (mean age, 44.8 ± 7.1 yr) participating in a 9-consecutive-day mountain cycling ultramarathon (TransPortugal) underwent anthropometric, hematological, and biochemical assessments before and immediately after the race. Participants were further stratified as completers (nine courses) or noncompleters and were divided according to the time they took to complete the race. The heme oxygenase-1 (HMOX1) functional genetic polymorphism and haptoglobin (HP) phenotypic variants were also analyzed. Total leukocytes, neutrophil count, and monocyte count increased, whereas decreases in erythrocyte counts and hemoglobin were found between pre- and postultramarathon. Circulating haptoglobin (Hp) was increased, whereas its soluble receptor (sCD163) decreased. Athletes who completed all nine courses presented with increased leukocyte, neutrophil, and erythrocyte counts, as well as hemoglobin, red cell distribution width, total bilirubin, and total cholesterol levels. High-sensitivity C-reactive protein and Hp decreased in comparison with noncompleters. HMOX1 and HP genetic polymorphisms were associated with biochemical profile, notably with Hp levels. Analysis of covariance showed a significant effect of HP phenotype in Hp circulating levels at the end of race and on the magnitude of variation from pre- to postrace. Present findings support a comodulatory influence of genetic- and exercise-associated factors on resulting inflammatory and hemoglobin catabolic marker Hp after highly demanding endurance exercise.

  15. Host inflammatory response to polypropylene implants: insights from a quantitative immunohistochemical and birefringence analysis in a rat subcutaneous model

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    Prudente, Alessandro; Fávaro, Wágner José; Latuf, Paulo; Riccetto, Cássio Luis Zanettini

    2016-01-01

    ABSTRACT Objectives To describe acute and sub acute aspects of histological and immunohistochemical response to PP implant in a rat subcutaneous model based on objective methods. Materials and Methods Thirty rats had a PP mesh subcutaneously implanted and the same dissection on the other side of abdomen but without mesh (sham). The animals were euthanized after 4 and 30 days. Six slides were prepared using the tissue removed: one stained with hematoxylin-eosin (inflammation assessment); one unstained (birefringence evaluation) and four slides for immunohistochemical processing: IL-1 and TNF-α (pro-inflammatory cytokines), MMP-2 (collagen metabolism) and CD-31 (angiogenesis). The area of inflammation, the birefringence index, the area of immunoreactivity and the number of vessels were objectively measured. Results A larger area of inflammatory reaction was observed in PP compared to sham on the 4th and on the 30th day (p=0.0002). After 4 days, PP presented higher TNF (p=0.0001) immunoreactivity than sham and no differences were observed in MMP-2 (p=0.06) and IL-1 (p=0.08). After 30 days, a reduction of IL-1 (p=0.010) and TNF (p=0.016) for PP and of IL-1 (p=0.010) for sham were observed. Moreover, area of MMP-2 immunoreactivity decreased over time for PP group (p=0.018). Birefringence index and vessel counting showed no differences between PP and sham (p=0.27 and p=0.58, respectively). Conclusions The implantation of monofilament and macroporous polypropylene in the subcutaneous of rats resulted in increased inflammatory activity and higher TNF production in the early post implant phase. After 30 days, PP has similar cytokines immunoreactivity, vessel density and extracellular matrix organization. PMID:27286125

  16. Molecular Interactions between NR4A Orphan Nuclear Receptors and NF-κB Are Required for Appropriate Inflammatory Responses and Immune Cell Homeostasis.

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    Murphy, Evelyn P; Crean, Daniel

    2015-06-29

    Appropriate innate and adaptive immune responses are essential for protection and resolution against chemical, physical or biological insults. Immune cell polarization is fundamental in orchestrating distinct phases of inflammation, specifically acute phase responses followed by resolution and tissue repair. Dysregulation of immune cell and inflammatory responses is a hallmark of multiple diseases encompassing atherosclerosis, rheumatoid arthritis, psoriasis and metabolic syndromes. A master transcriptional mediator of diverse inflammatory signaling and immune cell function is NF-κB, and altered control of this key regulator can lead to an effective switch from acute to chronic inflammatory responses. Members of the nuclear receptor (NR) superfamily of ligand-dependent transcription factors crosstalk with NF-κB to regulate immune cell function(s). Within the NR superfamily the NR4A1-3 orphan receptors have emerged as important regulators of immune cell polarization and NF-κB signaling. NR4A receptors modulate NF-κB activity in a dynamic fashion, either repressing or enhancing target gene expression leading to altered inflammatory outcome. Here we will discuss the pivotal role NR4A's receptors play in orchestrating immune cell homeostasis through molecular crosstalk with NF-κB. Specifically, we will examine such NR4A/NF-κB interactions within the context of distinct cell phenotypes, including monocyte, macrophage, T cells, endothelial, and mesenchymal cells, which play a role in inflammation-associated disease. Finally, we review the therapeutic potential of altering NR4A/NF-κB interactions to limit hyper-inflammatory responses in vivo.

  17. Wound trauma mediated inflammatory signaling attenuates a tissue regenerative response in MRL/MpJ mice

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    Elster Eric A

    2010-05-01

    Full Text Available Abstract Background Severe trauma can induce pathophysiological responses that have marked inflammatory components. The development of systemic inflammation following severe thermal injury has been implicated in immune dysfunction, delayed wound healing, multi-system organ failure and increased mortality. Methods In this study, we examined the impact of thermal injury-induced systemic inflammation on the healing response of a secondary wound in the MRL/MpJ mouse model, which was anatomically remote from the primary site of trauma, a wound that typically undergoes scarless healing in this specific strain. Ear-hole wounds in MRL/MpJ mice have previously displayed accelerated healing and tissue regeneration in the absence of a secondary insult. Results Severe thermal injury in addition to distal ear-hole wounds induced marked local and systemic inflammatory responses in the lungs and significantly augmented the expression of inflammatory mediators in the ear tissue. By day 14, 61% of the ear-hole wounds from thermally injured mice demonstrated extensive inflammation with marked inflammatory cell infiltration, extensive ulceration, and various level of necrosis to the point where a large percentage (38% had to be euthanized early during the study due to extensive necrosis, inflammation and ear deformation. By day 35, ear-hole wounds in mice not subjected to thermal injury were completely closed, while the ear-hole wounds in thermally injured mice exhibited less inflammation and necrosis and only closed partially (62%. Thermal injury resulted in marked increases in serum levels of IL-6, TNFα, KC (CXCL1, and MIP-2α (CXCL2. Interestingly, attenuated early ear wound healing in the thermally injured mouse resulted in incomplete tissue regeneration in addition to a marked inflammatory response, as evidenced by the histological appearance of the wound and increased transcription of potent inflammatory mediators. Conclusion These findings suggest that the

  18. Systemic inflammatory response syndrome (SIRS): where did it come from and is it still relevant today?

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    Balk, Robert A

    2014-01-01

    The concept of a systemic inflammatory response syndrome (SIRS) to describe the complex pathophysiologic response to an insult such as infection, trauma, burns, pancreatitis, or a variety of other injuries came from a 1991 consensus conference charged with the task of developing an easy-to-apply set of clinical parameters to aid in the early identification of potential candidates to enter into clinical trials to evaluate new treatments for sepsis. There was recognition that a diverse group of injuries produced a common inflammatory response in the host and provided attractive targets for new anti-inflammatory molecules designed to prevent further propagation and/or provide specific treatment. Effective application of these new anti-inflammatory strategies necessitated identification of early clinical markers that could be assessed in real-time and were likely to define a population of patients that would have a beneficial response to the targeted intervention. It was felt that early clinical manifestations might be more readily available to clinicians than more sophisticated and specific assays for inflammatory substances that were systemically released by the network of injurious inflammatory events. Therefore, the early definition of a systemic inflammatory response syndrome (SIRS) was built upon a foundation of basic clinical and laboratory abnormalities that were readily available in almost all clinical settings. With further refinement, it was hoped, that this definition would have a high degree of sensitivity, coupled with a reasonable degree of specificity. This manuscript reviews the derivation, application, utilization, potential benefits, and speculation regarding the future of the SIRS definition.

  19. Soluble Mediators in Platelet Concentrates Modulate Dendritic Cell Inflammatory Responses in an Experimental Model of Transfusion.

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    Perros, Alexis J; Christensen, Anne-Marie; Flower, Robert L; Dean, Melinda M

    2015-10-01

    The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose-associated suppression of the production of DC IL-12, IL-6, IL-1α, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein (MIP)-1β and storage-associated suppression of the production of DC IL-10, TNF-α, and IL-8. For the overall inflammatory response, IL-6, TNF-α, MIP-1α, MIP-1β, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1β significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications.

  20. An Unbalanced Inflammatory Cytokine Response Is Not Associated With Mortality Following Sepsis: A Prospective Cohort Study.

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    Frencken, Jos F; van Vught, Lonneke A; Peelen, Linda M; Ong, David S Y; Klein Klouwenberg, Peter M C; Horn, Janneke; Bonten, Marc J M; van der Poll, Tom; Cremer, Olaf L

    2017-05-01

    The prevailing theory of host response during sepsis states that an excessive production of pro-inflammatory mediators causes early deaths, whereas a predominantly anti-inflammatory response may lead to immunosuppression, secondary infection, and late deaths. We assessed inflammatory (im)balance by measuring pro-inflammatory interleukin-6 and anti-inflammatory interleukin-10 during three distinct time periods after sepsis, and assessed its association with mortality. Prospective observational cohort. Two tertiary mixed ICUs in The Netherlands. Consecutive patients presenting with severe sepsis or septic shock from 2011 to 2013. None. We repeatedly measured plasma interleukin-6 and interleukin-10 concentrations using cytometric bead array. Poisson regression was used to analyze the relation between inflammatory markers measured on 1) ICU admission and day 4 mortality, 2) day 4 and day 28 mortality, and 3) ICU discharge and 1-year mortality. Secondary outcome was development of ICU-acquired infections. Among 708 patients, 86 (12%) died within 4 days, 140 (20%) died between days 4 and 28, and an additional 155 (22%) died before 1 year. Interleukin-6 and interleukin-10 levels were both independently associated with mortality, but the balance of this response as modelled by an interleukin-6 and interleukin-10 interaction term was not (relative risk, 0.99; 95% CI, 0.95-1.04 on admission; relative risk, 1.02; 95% CI, 0.98-1.06 on day 4; and relative risk, 1.12; 95% CI, 0.98-1.29 at ICU discharge). However, inflammatory imbalance on day 4 was associated with development of ICU-acquired infections (subdistribution hazard ratio, 0.87; 95% CI, 0.77-0.98). Although both interleukin-6 and interleukin-10 productions are associated with death, the balance of these inflammatory mediators does not seem to impact either early, intermediate, or late mortality in patients presenting to the ICU with sepsis.

  1. CD8+effector memory T cells induce acute rejection of allogeneic heart retransplants in mice possibly through activating expression of inflammatory cytokines.

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    Du, Gang; Yang, Nuo; Gong, Wenlin; Fang, Yuan; He, Jian; Zhou, Nuo; Lu, Xiaoling; Zhao, Yongxiang

    2017-06-01

    To investigate the effects of CD8 + memory T (Tm) cells and CD8 + effector memory T (Tem) cells on the results of allogeneic heart retransplantations performed in mice. A skin transplantation model was used to generate sensitized splenic CD8 + Tem cells for infusion into BALB/c mice. One week after infusion, the BALB/c mice underwent allogeneic heart transplantation in the abdominal cavity. Cyclosporin A was administered via intraperitoneal injection starting one day prior to transplantation to arrest immunological rejection of the transplanted heart. The effects of sensitized CD8 + T em cells on allogeneic heart graft rejection were examined by monitoring survival of the transplanted hearts, the infiltration of effector memory CD8 + T cells into myocardium, and expressions of inflammatory cytokines in blood serum. Adoptive transfer of sensitized CD8 + Tem cells prior to transplantation induced an acute rejection response which decreased the survival of transplanted hearts. The rejection response was accompanied by an infiltration of CD8 + Tem cells into the transplanted myocardial tissue. Additionally, infusion of sensitized CD8 + Tem cells induced markedly increased expressions of IL-2 and IFN-γ, and decreased expression of TGF-β in the transplanted hearts, as well as higher levels of IFN-γ and CXCL-9 in blood serum. The infusion of sensitized CD8 + Tem cells induced an acute graft rejection response and decreased the survival of grafted hearts by regulating the expressions of inflammatory cytokines including CXCL-9, IL-2, and INF-γ. Cyclosporin A had no therapeutic effect on the graft rejection response induced by sensitized CD8 + Tem cells. Copyright © 2017. Published by Elsevier Inc.

  2. Diclofenac pretreatment effects on the toll-like receptor 4/nuclear factor kappa B-mediated inflammatory response to eccentric exercise in rat liver.

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    Barcelos, Rômulo Pillon; Bresciani, Guilherme; Rodriguez-Miguelez, Paula; Cuevas, Maria José; Soares, Félix Alexandre Antunes; Barbosa, Nilda Vargas; González-Gallego, Javier

    2016-03-01

    Acute exercise is a stress stimulus that may cause cell damage through the activation of the toll-like receptor (TLR)4 pathway, resulting in the translocation of nuclear factor kappa B (NF-κB) into the cell nucleus and the upregulation of inflammatory genes. Nonsteroidal anti-inflammatory drugs, such as diclofenac, are often prescribed to counteract exercise-induced inflammation. This study analyzed effects of diclofenac pretreatment on the TLR4/NF-κB pathway in rat liver after an acute eccentric exercise. Twenty male Wistar rats were divided in four groups: control-saline, control-diclofenac, exercise-saline and exercise-diclofenac. The rats received saline or diclofenac (10mg/kg) for 7days prior to an eccentric exercise bout. After exercise there was an increase in TLR4, myeloid differentiation primary response gene 88 (MyD88), TIR domain-containing adaptor inducing interferon (TRIF) and p65 NF-κB subunit protein levels. Exercise also resulted in increased mRNA and protein expression of interleukin (IL)-6, inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α. Proinflammatory effects of exercise were prevented by the administration of diclofenac, which blunted the activation of the TLR4/NF-κB pathway and the inflammatory response in the liver of exercised rats. Results from the present study highlight the role of TLR4 as a target for anti-inflammatory interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Pulmonary and systemic inflammatory responses in rabbits with gram-negative pneumonia.

    Science.gov (United States)

    Fox-Dewhurst, R; Alberts, M K; Kajikawa, O; Caldwell, E; Johnson, M C; Skerrett, S J; Goodman, R B; Ruzinski, J T; Wong, V A; Chi, E Y; Martin, T R

    1997-06-01

    The major goals of this study were to define the relationships between intrapulmonary and systemic inflammatory responses in animals with gram-negative pneumonia. We treated rabbits with intrapulmonary Escherichia coli (1 x 10(7) to 1 x 10(10) cfu/ml), and then measured physiologic, cellular, and molecular events in the lungs and systemic circulation for 24 h. The treatment protocols resulted in groups of animals that mimicked the stages of the septic inflammatory response in humans. Animals treated with low inocula had systemic changes consistent with systemic inflammatory response syndrome and cleared the bacteria and inflammatory products from the lungs. Animals treated with high inocula failed to clear bacteria from the lungs, had severe intrapulmonary inflammatory responses, and developed septic shock. Intrapulmonary leukocyte recruitment was directly related to the size of the bacterial inoculum, but lung protein accumulation was not. Tumor neurosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and GRO were detectable in lung lavage fluid at 4 h and declined by 24 h in animals that cleared intrapulmonary E. coli. In contrast, lavage TNF-alpha, IL-8, and GRO increased over 24 h in animals that failed to clear intrapulmonary bacteria. MCP-1 increased between 4 h and 24 h in the lungs of all of the animals as the histologic response evolved from neutrophilic to mononuclear cell predominance. Thus, the intensity of systemic inflammatory and physiologic responses to intrapulmonary gram-negative infection depends on the inoculum size and whether the bacteria are cleared from or proliferate in the lungs. The results provide experimental support for the recently proposed classification of septic responses in humans.

  4. Host transcription factors in the immediate pro-inflammatory response to the parasitic mite Psoroptes ovis.

    Directory of Open Access Journals (Sweden)

    Stewart T G Burgess

    Full Text Available BACKGROUND: Sheep scab, caused by infestation with the ectoparasitic mite Psoroptes ovis, results in the rapid development of cutaneous inflammation and leads to the crusted skin lesions characteristic of the disease. We described previously the global host transcriptional response to infestation with P. ovis, elucidating elements of the inflammatory processes which lead to the development of a rapid and profound immune response. However, the mechanisms by which this response is instigated remain unclear. To identify novel methods of intervention a better understanding of the early events involved in triggering the immune response is essential. The objective of this study was to gain a clearer understanding of the mechanisms and signaling pathways involved in the instigation of the immediate pro-inflammatory response. RESULTS: Through a combination of transcription factor binding site enrichment and pathway analysis we identified key roles for a number of transcription factors in the instigation of cutaneous inflammation. In particular, defined roles were elucidated for the transcription factors NF-kB and AP-1 in the orchestration of the early pro-inflammatory response, with these factors being implicated in the activation of a suite of inflammatory mediators. CONCLUSIONS: Interrogation of the host temporal response to P. ovis infestation has enabled the further identification of the mechanisms underlying the development of the immediate host pro-inflammatory response. This response involves key regulatory roles for the transcription factors NF-kB and AP-1. Pathway analysis demonstrated that the activation of these transcription factors may be triggered following a host LPS-type response, potentially involving TLR4-signalling and also lead to the intriguing possibility that this could be triggered by a P. ovis allergen.

  5. [The pathogenesis of the systemic inflammatory response syndrome and compensatory antiinflammatory response syndrome following surgical stress].

    Science.gov (United States)

    Ono, Satoshi; Ichikura, Takashi; Mochizuki, Hidetaka

    2003-07-01

    The inflammation charge cells such as the macrophages, neutrophils, endothelial cells, and fibroblasts are activated in surgical sites when tissue injury occurs due to the operation. Proinflammatory cytokines such as tumor necrosis factor alpha, interleukin (IL)-1, IL-6, and IL-8 are induced from the activated inflammation charge cells. These cytokines amplify the information by autocrine and paracrine action, induce the production of other cytokines, and send the information to the whole body. Increases in body temperature, pulse rate, and leukocyte counts are then observed. This condition is called the systemic inflammatory response syndrome (SIRS) clinically. On the other hand, the production of antiinflammatory cytokines against SIRS is induced simultaneously. The condition in which antiinflammatory cytokines are produced in excess and become dominant systemically is called the compensatory antiinflammatory response syndrome (CARS). No standard concrete diagnosis for CARS has been established, although CARS is a pathogenetic concept. However, recently the analysis of cytokine production and various types of surface molecules in the inflammation charge cells became possible with the development of molecular biological methods. As a result, it was found that the immune system is controlled by the balance between proinflammatory and antiinflammatory cytokine production, and if the compensatory antiinflammatory reaction is sufficiently severe, it will manifest clinically as anergy, with increased susceptibility to infection. In this manuscript, we explain the pathogenesis of SIRS and CARS following surgical stress by analyzing cytokine production and surface membrane molecules in the inflammation charge cells.

  6. Systemic inflammatory response syndrome increases immobility-induced neuromuscular weakness.

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    Fink, Heidrun; Helming, Marc; Unterbuchner, Christoph; Lenz, Andrea; Neff, Frauke; Martyn, J A Jeevendra; Blobner, Manfred

    2008-03-01

    Inflammation and immobility are comorbid etiological factors inducing muscle weakness in critically ill patients. This study establishes a rat model to examine the effect of inflammation and immobilization alone and in combination on muscle contraction, histology, and acetylcholine receptor regulation. Prospective, randomized, experimental study. Animal laboratory of a university hospital. Sprague-Dawley rats. To produce systemic inflammation, rats (n = 34) received three consecutive intravenous injections of Corynebacterium parvum on days 0, 4, and 8. Control rats (n = 21) received saline. Both groups were further divided to have one hind limb either immobilized by pinning of knee and ankle joints or sham-immobilized (surgical leg). The contralateral nonsurgical leg of each animal served as control (nonsurgical leg). After 12 days, body weight and muscle mass were significantly reduced in all C. parvum animals compared with saline-injected rats. Immobilization led to local muscle atrophy. Normalized to muscle mass, tetanic contraction was reduced in the surgical leg after immobilization (7.64 +/- 1.91 N/g) and after inflammation (8.71 +/- 2.0 N/g; both p < .05 vs. sham immobilization and saline injection, 11.03 +/- 2.26 N/g). Histology showed an increase in inflammatory cells in all C. parvum-injected animals. Immobilization in combination with C. parvum injection had an additive effect on inflammation. Acetylcholine receptors were increased in immobilized muscles and in all muscles of C. parvum-injected animals. The muscle weakness in critically ill patients can be replicated in our novel rat model. Inflammation and immobilization independently lead to muscle weakness.

  7. Increased levels of proteins of the acute inflammatory phase in the peritoneal fluid of women with advanced stages of endometriosis.

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    Polak, Grzegorz; Barczyński, Bartłomiej; Bednarek, Wiesława; Kwaśniewski, Wojciech; Wertell, Iwona; Derewianka-Polak, Magdalena; Makara-Studzińska, Marta; Kotarski, Jan

    2015-06-01

    Most investigators agree that endometriosis is associated with a state of subclinical, non-infectious peritoneal inflammation. The objective of the study was to assess concentrations of two markers of the acute inflammatory phase proteins, haptoglobin and ceruloplasmin, in peritoneal fluid of endometriotic women. 229 women who underwent diagnostic or therapeutic laparoscopy were included in the study Minimal, mild, moderate and severe endometriosis according to ASRM was confirmed in 119 women (study groups), whereas 110 patients suffered from simple serous or dermoid ovarian cysts (reference groups). Haptoglobin and ceruloplasmin concentrations in the peritoneal fluid samples aspirated during laparoscopy were measured using commercially available radial immunodiffusion kits. The concentration of haptoglobin in the peritoneal fluid of women with endometriosis was significantly higher as compared to patients with serous and dermoid ovarian cysts. Significantly higher haptoglobin level was observed in patients with severe and moderate endometriosis as compared to women from both reference groups. No significant difference in the peritoneal fluid ceruloplasmin levels was found between patients with endometriosis and women from reference groups. However, it was noted that ceruloplasmin levels are higher in the subgroup of patients with severe endometriosis as compared to both reference groups and women with mild disease. Our results support the hypothesis that endometriosis is associated with subclinical inflammation within the peritoneal cavity It may be speculated that pro-inflammatory stimuli strong enough to cause an increase in acute inflammatory phase proteins peritoneal fluid concentrations are observed only in the advanced stages of the disease.

  8. Abrogated inflammatory response promotes neurogenesis in a murine model of Japanese encephalitis.

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    Sulagna Das

    2011-03-01

    Full Text Available Japanese encephalitis virus (JEV induces neuroinflammation with typical features of viral encephalitis, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. The detrimental effects of inflammation on neurogenesis have been reported in various models of acute and chronic inflammation. We investigated whether JEV-induced inflammation has similar adverse effects on neurogenesis and whether those effects can be reversed using an anti-inflammatory compound minocycline.Here, using in vitro studies and mouse models, we observed that an acute inflammatory milieu is created in the subventricular neurogenic niche following Japanese encephalitis (JE and a resultant impairment in neurogenesis occurs, which can be reversed with minocycline treatment. Immunohistological studies showed that proliferating cells were replenished and the population of migrating neuroblasts was restored in the niche following minocycline treatment. In vitro, we checked for the efficacy of minocycline as an anti-inflammatory compound and cytokine bead array showed that production of cyto/chemokines decreased in JEV-activated BV2 cells. Furthermore, mouse neurospheres grown in the conditioned media from JEV-activated microglia exhibit arrest in both proliferation and differentiation of the spheres compared to conditioned media from control microglia. These effects were completely reversed when conditioned media from JEV-activated and minocycline treated microglia was used.This study provides conclusive evidence that JEV-activated microglia and the resultant inflammatory molecules are anti-proliferative and anti-neurogenic for NSPCs growth and development, and therefore contribute to the viral neuropathogenesis. The role of minocycline in restoring neurogenesis may implicate enhanced neuronal repair and attenuation of the neuropsychiatric sequelae in JE survivors.

  9. Response of Selenium and Selenogenome in Immune Tissues to LPS-Induced Inflammatory Reactions in Pigs.

    Science.gov (United States)

    Sun, Lv-Hui; Pi, Ding-An; Zhao, Ling; Wang, Xiu-Ying; Zhu, Luo-Yi; Qi, De-Sheng; Liu, Yu-Lan

    2017-05-01

    Circulating concentration of the essential trace element selenium (Se) was significantly lower in inflammatory disorders. Although Se plays physiological roles mainly through the function of 25 selenoproteins, the response of the selenogenome in immune tissues during inflammatory reactions remains unclear. The objective of this study was to determine the Se retention and selenogenome expression in immune tissues during the lipopolysaccharide (LPS)-induced inflammatory response in porcine. A total of 12 male pigs were randomly divided into two groups and injected with LPS or saline. After 4 h postinjection, blood samples were collected and pigs were euthanized. Pigs challenged with LPS had 36.8 and 16.6 % lower (P response of Txnrd2, Txnrd3, Sep15, Selh, Seli, Seln, Selo, Selt, Selx, and Sephs2 to inflammatory reaction in immune tissues were newly illustrated in this study. In conclusion, the LPS-induced inflammatory response impaired Se metabolism and was associated with dysregulation of the selenogenome expression in immune tissues.

  10. Triclosan Alters Anti-microbial and Inflammatory Responses of Epithelial Cells

    Science.gov (United States)

    Wallet, Mark A.; Calderon, Nadia L.; Alonso, Tess R.; Choe, Christina S.; Catalfamo, Dana L.; Lalane, Charles J.; Neiva, Kathleen G.; Panagakos, Foti; Wallet, Shannon M.

    2012-01-01

    Periodontal diseases are a class of pathologies wherein oral microbes induce harmful immune responses in a susceptible host. Therefore, an agent which can both reduce microbial burden and lessen pathogenesis of localized inflammation would have beneficial effects in periodontal disease. 2,4,4-trichloro-2-hydroxydiphenyl-ether [triclosan] is currently used in oral care products due to broad spectrum anti-microbial and anti-inflammatory properties. Objective To determine effects of triclosan on the response of oral epithelial cells to stimulation with the inflammatory microbial product lipopolysaccharide [LPS], a ligand for toll-like receptor 4 [TLR4]. Materials/Methods Primary human oral epithelial cells were stimulated with LPS in the presence and/or absence of triclosan after which expression of pro-inflammatory cytokines, β-defensins, micro-RNAs [miRNAs] or TLR signaling pathway proteins were evaluated. Results Here we demonstrate that triclosan is a potent inhibitor of oral epithelial cell LPS-induced pro-inflammatory responses by inducing miRNA regulation of the TLR-signaling pathway. Triclosan was not a pan-suppresser of oral epithelial cell responses as β-defensin 2 [βD2] and βD3 were upregulated by triclosan following LPS-stimulation. Conclusions These data demonstrate both a novel anti-microbial mechanism by which triclosan improves plaque control and an additional anti-inflammatory property which could have beneficial effects in periodontal disease resolution. PMID:24079913

  11. In vivo Anti-Inflammatory Effect of Zapoteca portoricensis (Jacq) HM ...

    African Journals Online (AJOL)

    Conclusion: Zapoteca portoricensis possesses significant anti-inflammatory activity in acute inflammation in rats. The terpenoids and steroids present in the column fractions may be responsible for the activity. Keywords: Zapoteca portoricensis; Anti-inflammatory, Egg albumeninduced edema, Terpenoids; Steroids.

  12. Early life socioeconomic status associates with interleukin-6 responses to acute laboratory stress in adulthood.

    Science.gov (United States)

    Lockwood, Kimberly G; John-Henderson, Neha A; Marsland, Anna L

    2018-05-01

    It is proposed that environmental exposures in early life influence immune programming. Specifically, socioeconomic disadvantage is thought to program an immune phenotype that is prone to inflammation and associated with increased risk for inflammatory disease later in life. Existing literature shows an inverse association of early childhood socioeconomic status (SES) with adult levels of systemic inflammation. Here, we extend that literature to examine whether early childhood SES also relates to the magnitude of inflammatory response to acute psychological stress in adulthood. Healthy volunteers (N = 110; 40-58 years; 59% female; 90% white) performed a laboratory stress protocol, with blood samples drawn at the end of a 30-min baseline, a 5-min speech task, and a 30-min recovery to assess interleukin (IL)-6 stress responses. An early childhood SES index was derived from reports of parental home and vehicle ownership, and number of bedrooms per child in the home across ages 1-2, 3-4, and 5-6. Regressions adjusted for current age, sex, race, and BMI showed that lower SES at age 1-2 was associated with larger IL-6 stress responses in adulthood (ΔR 2  = 0.05, β = -0.24, p = .03). This association was independent of adult SES and task-evoked affective responses. No association was found between SES at ages 3-4 or 5-6 and IL-6 responses. These results provide initial evidence for a link between disadvantage in the first 2 years of life and heightened inflammatory response to stress in adulthood; this link may contribute to the increased disease risk that accompanies being raised in disadvantaged socioeconomic circumstances. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Scuba diving induces nitric oxide synthesis and the expression of inflammatory and regulatory genes of the immune response in neutrophils.

    Science.gov (United States)

    Sureda, Antoni; Batle, Juan M; Capó, Xavier; Martorell, Miquel; Córdova, Alfredo; Tur, Josep A; Pons, Antoni

    2014-09-01

    Scuba diving, characterized by hyperoxia and hyperbaria, could increase reactive oxygen species production which acts as signaling molecules to induce adaptation against oxidative stress. The aim was to study the effects of scuba diving immersion on neutrophil inflammatory response, the induction of oxidative damage, and the NO synthesis. Nine male divers performed a dive at 50 m depth for a total time of 35 min. Blood samples were obtained at rest before the dive, after the dive, and 3 h after the diving session. Markers of oxidative and nitrosative damage, nitrite, and the gene expression of genes related with the synthesis of nitric oxide and lipid mediators, cytokine synthesis, and inflammation were determined in neutrophils. The mRNA levels of genes related with the inflammatory and immune response of neutrophils, except TNF-α, myeloperoxidase, and toll-like receptor (TLR) 2, significantly increased after the recovery period respect to predive and postdive levels. NF-κB, IL-6, and TLR4 gene expression reported significant differences immediately after diving respect to the predive values. Protein nitrotyrosine levels significantly rose after diving and remained high during recovery, whereas no significant differences were reported in malondialdehyde. Neutrophil nitrite levels as indicative of inducible nitric oxide synthase (iNOS) activity progressively increased after diving and recovery. The iNOS protein levels maintained the basal values in all situations. Scuba diving which combines hyperoxia, hyperbaria, and acute exercise induces nitrosative damage with increased nitrotyrosine levels and an inflammatory response in neutrophils. Copyright © 2014 the American Physiological Society.

  14. Fluoro-edenite Fibers Induce Expression of Hsp70 and Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Michael Balazy

    2007-09-01

    Full Text Available Many asbestos-like mineral fibers have been detected in the air of mountainous and volcanic areas of Italy and other parts of the world. These fibers have been suspected to be the cause of increased incidences of lung cancer and other lung diseases in these areas. However, the mechanisms of the cellular response and defense following exposure to these microscopic fibers have not been characterized. We continue to study these mechanisms to be able to propose preventive strategies in large populations. The objective of the present study was to determine comparatively biological r