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Sample records for epicutaneous sensitization-induced inflammation

  1. ST2 Requires Th2-, but Not Th17-, Type Airway Inflammation in Epicutaneously Antigen-Sensitized Mice

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    Hideaki Morita

    2012-01-01

    Conclusions: The IL-33/ST2 pathway is crucial for Th2-cytokine-mediated eosinophilic, rather than Th17-cytokine-mediated neutrophilic, airway inflammation in mice that had been epicutaneously sensitized with antigens and then challenged with antigen.

  2. Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation.

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    Philipp R Esser

    Full Text Available BACKGROUND: Allergic contact dermatitis (ACD represents a severe health problem with increasing worldwide prevalence. It is a T cell-mediated skin disease induced by protein-reactive organic and inorganic chemicals. A key feature of contact allergens is their ability to trigger an innate immune response that leads to skin inflammation. Previous evidence from the mouse contact hypersensitivity (CHS model suggests a role for endogenous activators of innate immune signaling. Here, we analyzed the role of contact sensitizer induced ROS production and concomitant changes in hyaluronic acid metabolism on CHS responses. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed in vitro and in vivo ROS production using fluorescent ROS detection reagents. HA fragmentation was determined by gel electrophoresis. The influence of blocking ROS production and HA degradation by antioxidants, hyaluronidase-inhibitor or p38 MAPK inhibitor was analyzed in the murine CHS model. Here, we demonstrate that organic contact sensitizers induce production of reactive oxygen species (ROS and a concomitant breakdown of the extracellular matrix (ECM component hyaluronic acid (HA to pro-inflammatory low molecular weight fragments in the skin. Importantly, inhibition of either ROS-mediated or enzymatic HA breakdown prevents sensitization as well as elicitation of CHS. CONCLUSIONS/SIGNIFICANCE: These data identify an indirect mechanism of contact sensitizer induced innate inflammatory signaling involving the breakdown of the ECM and generation of endogenous danger signals. Our findings suggest a beneficial role for anti-oxidants and hyaluronidase inhibitors in prevention and treatment of ACD.

  3. Epicutaneous sensitization with protein antigen

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    I-Lin Liu

    2012-12-01

    Full Text Available In the past few decades there has been a progressive understanding that epicutaneous sensitization with protein antigen is an important sensitization route in patients with atopic dermatitis. A murine protein-patch model has been established, and an abundance of data has been obtained from experiments using this model. This review discusses the characteristics of epicutaneous sensitization with protein antigen, the induced immune responses, the underlying mechanisms, and the therapeutic potential.

  4. Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy.

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    Hussain, Maryam; Borcard, Loïc; Walsh, Kevin P; Pena Rodriguez, Maria; Mueller, Christoph; Kim, Brian S; Kubo, Masato; Artis, David; Noti, Mario

    2017-04-06

    Exaggerated thymic stromal lymphopoietin (TSLP) production and infiltration of basophils are associated with the pathogenesis of atopic dermatitis (AD), a recognized risk factor for the development of food allergies. Although TSLP and basophils have been implicated in promotion of food-induced allergic disorders in response to epicutaneous sensitization, the mechanisms by which TSLP-elicited basophils guide the progression of allergic inflammation in the skin to distant mucosal sites, such as the gastrointestinal tract, are poorly understood. We sought to test the role of basophil-intrinsic IL-4 production in TH2 sensitization to food antigens in the skin and effector food-induced allergic responses in the gut. Mice were epicutaneously sensitized with ovalbumin on an AD-like skin lesion, followed by intragastric antigen challenge to induce IgE-mediated food allergy. The requirement for basophil-derived IL-4 production for TH2 polarization and the pathogenesis of IgE-mediated food allergy was assessed in vitro by using coculture experiments with naive T cells and in vivo by using Il4 3'UTR mice that selectively lack IL-4 production in basophils. Epicutaneous food antigen sensitization is associated with infiltration of IL-4-competent innate immune cells to the skin, with basophils and eosinophils representing the predominant populations. In contrast to basophils, absence of eosinophils did not alter disease outcome. Coculture of IL-4-competent basophils together with dendritic cells and naive T cells was sufficient to promote TH2 polarization in an IL-4-dependent manner in vitro, whereas absence of basophil-intrinsic IL-4 production in vivo was associated with reduced food-induced allergic responses. TSLP-elicited basophils promote epicutaneous sensitization to food antigens and subsequent IgE-mediated food allergy through IL-4. Strategies to target the TSLP-basophil-IL-4 axis in patients with AD might lead to innovative therapies that can prevent the

  5. Antigen-driven bystander effect accelerates epicutaneous sensitization with a new protein allergen

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    Yu Jhang-Sian

    2009-03-01

    Full Text Available Abstract Exposure to protein allergen epicutaneously, inducing a Th2-dominant immune response, sensitizes the host to the development of atopic disease. Antigen-driven bystander effect demonstrates that polarized T cells could instruct naïve T cells to differentiate into T cells with similar phenotype. In this study, we aimed to determine the contribution of antigen-driven bystander effect on epicutaneous sensitization with a newly introduced protein allergen. BALB/c mice were immunized intraperitoneally with BSA emulsified in alum, known to induce a Th2 response, three weeks before given BSA and OVA epicutaneously. Lymph node cells from these mice restimulated with OVA secreted higher levels IL-4, IL-5 and IL-13 as compared with cells from mice without BSA immunization. In addition, BALB/c mice immunized subcutaneously with BSA emulsified in complete Freund's adjuvant, known to induce a Th1-predominant response, also induced higher Th1 as well as Th2 cytokine response when restimulated with OVA as compared with mice without immunization. We demonstrated that subcutaneous immunization with BSA in CFA induced Th2 as well as Th1 response. The threshold of epicutaneous sensitization to OVA was also reduced, possibly due to increased expressions of IL-4 and IL-10 in the draining lymph nodes during the early phase of sensitization. In conclusion, antigen-driven bystander effect, whether it is of Th1- or Th2-predominant nature, can accelerate epicutaneous sensitization by a newly introduced protein allergen. These results provide a possible explanation for mono- to poly-sensitization spread commonly observed in atopic children.

  6. Inflammation

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    Holst-Hansen, Thomas

    Inflammation is an intricate response relying on the activation and response of both the innate immune system and the infected tissue to remove a threat. The pro-inflammatory NF-kappaB pathway has been studied extensively, among others because of its key role in regulation of inflammation. However...

  7. Food allergy preceded by contact urticaria due to the same food: Involvement of epicutaneous sensitization in food allergy

    National Research Council Canada - National Science Library

    Inomata, Naoko; Nagashima, Mayumi; Hakuta, Amiko; Aihara, Michiko

    2015-01-01

    .... To clarify the role of epicutaneous sensitization in food allergy, we investigated the clinical characteristics of adult patients with food allergies preceded by contact urticaria due to the same foods.Methods...

  8. Epicutaneous Administration of Papain Induces IgE and IgG Responses in a Cysteine Protease Activity-Dependent Manner

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    Hideo Iida

    2014-01-01

    Conclusions: We demonstrated that the epicutaneous administration of protease not only disrupted skin barrier function, but also induced IgE and IgG responses in a manner dependent on its protease activity. These results suggest that protease activity contained in environmental sources contributes to sensitization through an epicutaneous route.

  9. [Epicutaneous patch testing in delayed drug hypersensitivity reactions induced by antiepileptic drugs].

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    Ben Mahmoud, Lobna; Bahloul, Najla; Ghozzi, Hanen; Kammoun, Brahim; Hakim, Ahmed; Sahnoun, Zouheir; Kammoun, Sami; Zeghal, Khaled

    2017-10-01

    Antiepileptic drugs are widely used and are associated with numerous side effects including skin eruptions. Epicutaneous tests have been used with variable success in skin drug reactions. The purpose of this study was to evaluate the profitability of epicutaneous tests in delayed hypersensitivity reactions induced by antiepileptic drugs. We analyzed all cases of allergic skin reactions to antiepileptic drugs notified in regional pharmacovigilance center of Sfax (Tunisia) between June 1, 2014 and April 30, 2016. The imputation score, determined using the French imputation method, should be at least doubtful. Patch-tests were performed in accordance with the general Europen network on Drug Allergy/European Academy of Allergy and Clinical Immunology (ENDA/EAACI) guidelines. Patch-tests were read according to the generally accepted criteria of the International contact dermatitis research group (ICDRG). In our study, 20 patients were included, among which 23 events were observed. The drug involved in delayed hypersensitivity reactions was carbamazepine in 11 cases, phenobarbital in 10 cases and valproic acid in 4 cases. The clinical reactions caused by the drug were classified as maculopapular exanthema (11 cases), DRESS syndrome (6 cases), Stevens-Johnson syndrome (2 cases), fixed drug eruption (2 cases) and erythroderma (2 cases). Patch-tests were positive in 19 patients (95 %). Cross-reactivity between antiepileptic drugs was observed in 4 cases: between valproic acid and carbamazepine in 2 cases between valproic acid and phenobarbital in 1 case and between phenobarbital and carbamazepine in 1 case. In this study, patch testing was a safe and useful method in confirming the culprit drug in delayed hypersensitivity reactions induced by antiepileptic drugs. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  10. THE FIRST BULGARIAN STANDARDIZED SERIES FOR EPICUTANEOUS PATCH TESTING FOR ALLERGIES TO DENTAL MATERIALS AND ALLOYS

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    Maria Dencheva

    2012-07-01

    Full Text Available The teeth and teeth rows restoration in the maxillofacial area is the last stage of the ongoing patient treatment and a basic purpose for the dental doctors. For this purpose a different set of modern and classic contemporary dental materials is used. The choice of each material during the treatment of every patient with proven allergy to different kind of allergens is very specific and strictly individual. In the everyday oral diagnostics a standardized set of allergens for diagnostics is used for proving the allergy to dental materials. The set has been developed on the base of all existing and permitted by the Bulgarian authorities dental materials, as well as professional series.The difference between the developed and standardized allergens for diagnostics used in our country and the existing ready-for-use series is that the first are made of the final product (material in the form introduced to the oral cavity and persisting there for a different period of time, sometimes for tenths of years. This enables the possibility for early or late contact allergic reactions with symptoms in the oral cavity and on the skin, maxillofacial area, head and neck, as well as the entire organism.The current article introduces the readers to the results obtained by the realization of the research project №28/2011 “Research on the type of sensibilisation to contemporary dental materials and development of set of allergens for its diagnosing through epicutaneous patch testing” funded by the Committee of Medical science of MU Sofia (CMC. Through the project became possible the creation and the initial research of the first Bulgarian series for epicutaneous testing whose aim is to prove the allergenic potential of the most frequently used by the dental doctors dental materials.

  11. Epicutaneous exposure to nickel induces nickel allergy in mice via a MyD88-dependent and interleukin-1-dependent pathway

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    Vennegaard, Marie T; Dyring-Andersen, Beatrice; Skov, Lone

    2014-01-01

    of nickel in the epidermis, and induces nickel allergy in mice. The allergic response to nickel following epicutaneous exposure is MyD88-dependent and interleukin (IL)-1 receptor-dependent, but independent of toll-like receptor (TLR)-4. CONCLUSION: This new model for nickel allergy that reflects...... epicutaneous exposure to nickel in humans shows that nickel allergy is dependent on MyD88 and IL-1 receptor signalling, but independent of TLR4....

  12. Food allergy preceded by contact urticaria due to the same food: involvement of epicutaneous sensitization in food allergy.

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    Inomata, Naoko; Nagashima, Mayumi; Hakuta, Amiko; Aihara, Michiko

    2015-01-01

    There have recently been reports suggesting that sensitization to food allergens may occur outside the intestinal tract, especially through the skin. To clarify the role of epicutaneous sensitization in food allergy, we investigated the clinical characteristics of adult patients with food allergies preceded by contact urticaria due to the same foods. We investigated clinical characteristics of 15 patients (20-51 years of age; 5 men and 10 women), who had food allergies preceded by contact urticaria. Fourteen patients were contact urticaria due to the causative foods during occupationally cooking, whereas 1 patient during face pack. In the occupational group, causative foods included rice, wheat, fruits, vegetables, fish, shrimp and cuttlefish; in the fresh cucumber paste case the cause was cucumber. In the 15 patients, the causative foods were fresh, not processed, and were tolerated by most (9/15, 60%) after heating. Regarding to symptoms after ingestion of the causative foods, the most frequently induced symptoms was oral symptoms (14/15, 93.3%), followed by urticaria (4/15, 26.7%), abdominal symptoms (3/15, 20%). The duration between the start of jobs or face pack, and the onset of contact urticaria was from 1 month to 19 years (mean, 8.7 years). The duration between the onset of contact urticaria and the onset of food allergy was from a few weeks to 6 years (mean, 11 months). One sushi cook experienced severe anaphylactic shock after ingestion of fish. In the occupational group, 13 of 15 patients (86.7%) had atopic dermatitis or hand eczema, indicating that the impaired skin barrier might be a risk for food allergies induced by epicutaneous sensitization. Epicutaneous sensitization of foods could induce food allergy under occupational cooking and skin-care treatment with foods in adults. Copyright © 2014 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  13. Epicutaneous immunotherapy (EPIT blocks the allergic esophago-gastro-enteropathy induced by sustained oral exposure to peanuts in sensitized mice.

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    Lucie Mondoulet

    Full Text Available BACKGROUND: Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT on these processes. METHODS: Mice were sensitized by gavages with whole peanut protein extract (PPE given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure. RESULTS: Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm(2 and reduced villus/crypt ratios (1.6±0.15. In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines as well as esophageal eosinophilia (50 eosinophils/mm(2, p<0.05, mRNA expression of Th2 cytokines in tissue--eotaxin (p<0.05, IL-5 (p<0.05, and IL-13 (p<0.05--GATA-3 (p<0.05, and intestinal villus sub-atrophia (2.3±0.15. EPIT also increased specific IgG2a (p<0.05 and mRNA expression of Foxp3 (p<0.05 in the esophageal mucosa. CONCLUSIONS: Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT.

  14. Retroperitoneal inflammation

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    ... page: //medlineplus.gov/ency/article/001255.htm Retroperitoneal inflammation To use the sharing features on this page, please enable JavaScript. Retroperitoneal inflammation is swelling that occurs in the retroperitoneal space. ...

  15. Hyperbaric oxygen therapy attenuates central sensitization induced by a thermal injury in humans

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    Rasmussen, V M; Borgen, A E; Jansen, E C

    2015-01-01

    BACKGROUND: Hyperbaric oxygen (HBO2 ) treatment has in animal experiments demonstrated antinociceptive effects. It was hypothesized that these effects would attenuate secondary hyperalgesia areas (SHAs), an expression of central sensitization, after a first-degree thermal injury in humans. METHODS...... was demonstrated. However, in the nine volunteers starting with the control session, a statistical significant attenuation of SHAs was demonstrated in the HBO2 session (P = 0.004). CONCLUSIONS: The results indicate that HBO2 therapy in humans attenuates central sensitization induced by a thermal skin injury......, compared with control. These new and original findings in humans corroborate animal experimental data. The thermal injury model may give impetus to future human neurophysiological studies exploring the central effects of hyperbaric oxygen treatment....

  16. Epidermal Expression of Intercellular Adhesion Molecule 1 is Not a Primary Inducer of Cutaneous Inflammation in Transgenic Mice

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    Williams, Ifor R.; Kupper, Thomas S.

    1994-10-01

    Keratinocytes at sites of cutaneous inflammation have increased expression of intercellular adhesion molecule 1 (ICAM-1), a cytokine-inducible adhesion molecule which binds the leukocyte integrins LFA-1 and Mac-1. Transgenic mice were prepared in which the expression of mouse ICAM-1 was targeted to basal keratinocytes by using the human K14 keratin promoter. The level of constitutive expression attained in the transgenic mice exceeded the peak level of ICAM-1 expression induced on nontransgenic mouse keratinocytes in vitro by optimal combinations of interferon γ and tumor necrosis factor α or in vivo by proinflammatory stimuli such as phorbol 12-myristate 13-acetate. In vitro adhesion assays demonstrated that cultured transgenic keratinocytes were superior to normal keratinocytes as a substrate for the LFA-1-dependent binding of mouse T cells, confirming that the transgene-encoded ICAM-1 was expressed in a functional form. However, the high level of constitutive ICAM-1 expression achieved on keratinocytes in vivo in these transgenic mice did not result in additional recruitment of CD45^+ leukocytes into transgenic epidermis, nor did it elicit dermal inflammation. Keratinocyte ICAM-1 expression also did not potentiate contact-hypersensitivity reactions to epicutaneous application of haptens. The absence of a spontaneous phenotype in these transgenic mice was not the result of increased levels of soluble ICAM-1, since serum levels of soluble ICAM-1 were equal in transgenic mice and controls. We conclude that elevated ICAM-1 expression on keratinocytes cannot act independently to influence leukocyte trafficking and elicit cutaneous inflammation.

  17. Inflammation and Heart Disease

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    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Inflammation and Heart Disease Updated:Jun 13,2017 Understand the risks of inflammation. Although it is not proven that inflammation causes ...

  18. Inflammation of the Penis

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    ... Shrinks Testicles in Mice Additional Content Medical News Inflammation of the Penis (Balanitis; Posthitis; Balanoposthitis) By Patrick ... Penile and Testicular Disorders Epididymitis and Epididymo-orchitis Inflammation of the Penis Orchitis Peyronie Disease Phimosis and ...

  19. Inflammation of the Orbit

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    ... Glaucoma (Video) Macular Degeneration Additional Content Medical News Inflammation of the Orbit (Inflammatory Orbital Pseudotumor) By James ... Introduction to Eye Socket Disorders Cavernous Sinus Thrombosis Inflammation of the Orbit Orbital Cellulitis Preseptal Cellulitis Tumors ...

  20. Inflammation and coagulation

    NARCIS (Netherlands)

    Levi, Marcel; van der Poll, Tom

    2010-01-01

    In the pathogenesis of sepsis, inflammation and coagulation play a pivotal role. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation leads to activation of coagulation, and coagulation also considerably affects inflammatory activity. Molecular

  1. From inflammation to cancer.

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    Korniluk, A; Koper, O; Kemona, H; Dymicka-Piekarska, V

    2017-02-01

    The participation of inflammation in the progression of cancer for many years have been the subject of research. In the 19th century, there was evidence that an acute inflammation may inhibit the development of cancer. However, chronic inflammation affects the progression of the disease. Today, it is known that inflammation and cancer use similar mechanisms of development such as severe cell proliferation or angiogenesis. It has been shown that prolonged presence of inflammatory cells and factors in the tumor microenvironment can accelerate its growth and inhibit apoptosis of transformed cells. In this article we present a brief history of the discovery mechanisms and potential links between acute and chronic inflammation and cancer.

  2. Wnt/β-catenin signaling modulates human airway sensitization induced by β2-adrenoceptor stimulation.

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    Christophe Faisy

    Full Text Available BACKGROUND: Regular use of β2-agonists may enhance non-specific airway responsiveness. The wingless/integrated (Wnt signaling pathways are responsible for several cellular processes, including airway inflammation and remodeling while cAMP-PKA cascade can activate the Wnt signaling. We aimed to investigate whether the Wnt signaling pathways are involved in the bronchial hyperresponsiveness induced by prolonged exposure to β2-adrenoceptor agonists in human isolated airways. METHODS: Bronchi were surgically removed from 44 thoracic surgery patients. After preparation, bronchial rings and primary cultures of bronchial epithelial cells were incubated with fenoterol (0.1 µM, 15 hours, 37 °C, a β2-agonist with high intrinsic efficacy. The effects of inhibitors/blockers of Wnt signaling on the fenoterol-induced airway sensitization were examined and the impact of fenoterol exposure on the mRNA expression of genes interacting with Wnt signaling or cAMP-PKA cascade was assessed in complete bronchi and in cultured epithelial cells. RESULTS: Compared to paired controls, fenoterol-sensitization was abolished by inhibition/blockage of the Wnt/β-catenin signaling, especially the cell-surface LRP5/6 co-receptors or Fzd receptors (1 µM SFRP1 or 1 µM DKK1 and the nuclear recruitment of TCF/LEF transcriptions factors (0.3 µM FH535. Wnt proteins secretion did not seem to be involved in the fenoterol-induced sensitization since the mRNA expression of Wnt remained low after fenoterol exposure and the inactivator of Wnt secretion (1 µM IWP2 had no effect on the fenoterol-sensitization. Fenoterol exposure did not change the mRNA expression of genes regulating Wnt signaling or cAMP-PKA cascade. CONCLUSIONS: Collectively, our pharmacological investigations indicate that fenoterol-sensitization is modulated by the inhibition/blockage of canonical Wnt/β-catenin pathway, suggesting a phenomenon of biased agonism in connection with the β2-adrenoceptor stimulation

  3. Inflammation and axon regeneration.

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    Benowitz, Larry I; Popovich, Phillip G

    2011-12-01

    The inflammatory response that accompanies neural injury involves multiple cell types and effector molecules with both positive and negative effects. Inflammation is essential for normal regeneration in the peripheral nervous system, and here we review evidence that augmenting inflammation can enhance regeneration in areas of the central nervous system in which it normally does not occur. Within the spinal cord, inflammation enables transplanted sensory neurons to regenerate lengthy axons and enhances the ability of a trophic factor to promote corticospinal tract sprouting. Induction of inflammation in the eye supports survival of retinal ganglion cells and enables them to regenerate injured axons through the optic nerve. These effects are linked to an atypical trophic factor, oncomodulin, along with other, better known molecules. Induction of inflammation within dorsal root ganglia, when combined with other treatments, enables peripheral sensory neurons to regenerate axons into the spinal cord. However, inflammation also has negative effects that impede recovery. In light of the importance of inflammation for neural repair, it is important to identify the specific cell types and molecules responsible for the positive and negative effects of inflammation and to develop treatments that tip the balance to favor repair.

  4. Analysis of the use of fenthion via epicutaneous in dogs for Rhipicephalus sanguineus control Análise do uso de fenthion via epicutânea em cães para o controle de Rhipicephalus sanguineus

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    Fernando de Freitas Fernandes

    2001-01-01

    Full Text Available The action of fenthion was studied in a 15% epicutaneous formulation upon Rhipicephalus sanguineus, which may transmit pathogens to men and other animals, such as Ehrlichia, Babesia and Ricketsia. Dogs were artificially infected for the trial. The fenthion bioassays were begun four months after artificial infestation. The test group, having a mean of 186 ticks per dog, received the formulation dosage according to body weight on the neck region. Tick counts were performed, considering diameters > or = 2mm, during 11 days of treatment, in the most affected body areas: back, ears and paws. Before the application of fenthion in the dogs, it were observed an average 43.3% ticks in the ears, 38.1% in the back area and 17.6% in the paws. The number of ticks in dogs decreased by 36.2%, 63.8%, 82.7%, 67%, 40% and 4.9%, respectively on days 1, 2, 3, 5, 7, 9 and 11 after treatment. R. sanguineus anti-tick activity, lower than that officially recommended, was verified. The number of ticks increased progressively after the 5th day, demonstrating residual insecticide inefficacy. The results obtained did not indicate the use of this formulation, at the tested dosage, as an elective measure for R. sanguineus control.Investigou-se a atividade de fenthion em formulação epicutânea a 15% sobre Rhipicephalus sanguineus, transmissor de patógenos ao homem e animais, tais como Ehrlichia, Babesia e Ricketsia. Infestou-se artificialmente cães com larvas deste carrapato. Os bioensaios com o fenthion iniciaram-se 4 meses após a infestação artificial. Constatada a média de 186 ixodídeos/cão, cães do grupo teste receberam na região da nuca a dosagem correspondente ao seu peso. Avaliaram-se a eficiência e a atividade residual através de contagens dos carrapatos com diâmetro > ou = 2mm, durante 11 dias, nas áreas corpóreas mais parasitadas: dorso, orelhas e patas. Anteriormente, à aplicação do fenthion, 44,3% dos carrapatos format observados nas orelhas

  5. Hypoxia and Mucosal Inflammation

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    Colgan, Sean P.; Campbell, Eric L.; Kominsky, Douglas J.

    2016-01-01

    Sites of inflammation are defined by significant changes in metabolic activity. Recent studies have suggested that O2 metabolism and hypoxia play a prominent role in inflammation so-called “inflammatory hypoxia,” which results from a combination of recruited inflammatory cells (e.g., neutrophils and monocytes), the local proliferation of multiple cell types, and the activation of multiple O2-consuming enzymes during inflammation. These shifts in energy supply and demand result in localized regions of hypoxia and have revealed the important function off the transcription factor HIF (hypoxia-inducible factor) in the regulation of key target genes that promote inflammatory resolution. Analysis of these pathways has provided multiple opportunities for understanding basic mechanisms of inflammation and has defined new targets for intervention. Here, we review recent work addressing tissue hypoxia and metabolic control of inflammation and immunity. PMID:27193451

  6. Inflammation and cancer

    National Research Council Canada - National Science Library

    Noemí Eiró Francisco J Vizoso

    2012-01-01

    ... to cancer.An unresolved inflammation due to any failure in the precise control of the immune response can continue to perturb the cellular microenvironment, thereby leading to alterations in cancer-related...

  7. Inflammation, Immunity, and Hypertension

    National Research Council Canada - National Science Library

    Arisya Agita; M Thaha Alsagaff

    2017-01-01

    The immune system, inflammation and hypertension are related to each other. Innate and adaptive immunity system triggers an inflammatory process, in which blood pressure may increase, stimulating organ damage...

  8. Fundamentals of inflammation

    National Research Council Canada - National Science Library

    Serhan, Charles N; Ward, Peter A; Gilroy, Derek W

    2010-01-01

    .... Uncontrolled inflammation has emerged as a pathophysiologic basis for many widely occurring diseases in the general population that were not initially known to be linked to the inflammatory response...

  9. Inflammation and Insulin Resistance

    OpenAIRE

    de Luca, Carl; Olefsky, Jerrold M.

    2007-01-01

    Obesity-induced chronic inflammation is a key component in the pathogenesis of insulin resistance and the Metabolic syndrome. In this review, we focus on the interconnection between obesity, inflammation and insulin resistance. Pro-inflammatory cytokines can cause insulin resistance in adipose tissue, skeletal muscle and liver by inhibiting insulin signal transduction. The sources of cytokines in insulin resistant states are the insulin target tissue themselves, primarily fat and liver, but t...

  10. Obesity, Inflammation, and Cancer

    OpenAIRE

    Deng, Tuo; Lyon, Christopher J.; Bergin, Stephen; Michael A. Caligiuri; Hsueh, Willa A.

    2016-01-01

    Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including cancer, and is increasingly recognized as a growing cause of preventable cancer risk. Chronic inflammation, a well-known mediator of cancer, is a central characteristic of obesity, leading to many of its complications, and obesity-induced inflammation confers additional cancer risk beyond obesity itself. Multiple mechanisms facilitate this strong association between cancer and ob...

  11. Inflammation in Diabetic Nephropathy

    OpenAIRE

    Lim, Andy K. H.; Tesch, Gregory H.

    2012-01-01

    Diabetic nephropathy is the leading cause of end-stage kidney disease worldwide but current treatments remain suboptimal. This review examines the evidence for inflammation in the development and progression of diabetic nephropathy in both experimental and human diabetes, and provides an update on recent novel experimental approaches targeting inflammation and the lessons we have learned from these approaches. We highlight the important role of inflammatory cells in the kidney, particularly i...

  12. PPARs, Obesity, and Inflammation

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    Rinke Stienstra

    2007-01-01

    Full Text Available The worldwide prevalence of obesity and related metabolic disorders is rising rapidly, increasing the burden on our healthcare system. Obesity is often accompanied by excess fat storage in tissues other than adipose tissue, including liver and skeletal muscle, which may lead to local insulin resistance and may stimulate inflammation, as in steatohepatitis. In addition, obesity changes the morphology and composition of adipose tissue, leading to changes in protein production and secretion. Some of these secreted proteins, including several proinflammatory mediators, may be produced by macrophages resident in the adipose tissue. The changes in inflammatory status of adipose tissue and liver with obesity feed a growing recognition that obesity represents a state of chronic low-level inflammation. Various molecular mechanisms have been implicated in obesity-induced inflammation, some of which are modulated by the peroxisome proliferator-activated receptors (PPARs. PPARs are ligand-activated transcription factors involved in the regulation of numerous biological processes, including lipid and glucose metabolism, and overall energy homeostasis. Importantly, PPARs also modulate the inflammatory response, which makes them an interesting therapeutic target to mitigate obesity-induced inflammation and its consequences. This review will address the role of PPARs in obesity-induced inflammation specifically in adipose tissue, liver, and the vascular wall.

  13. Where Does Inflammation Fit?

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    Biasucci, Luigi M; La Rosa, Giulio; Pedicino, Daniela; D'Aiello, Alessia; Galli, Mattia; Liuzzo, Giovanna

    2017-09-01

    This review focuses on the complex relationship between inflammation and the onset of acute coronary syndrome and heart failure. In the last few years, two important lines of research brought new and essential information to light in the pathogenesis of acute coronary syndrome: a) the understanding of the immune mediate mechanisms of inflammation in Ischemic Heart Disease (IHD) and b) evidence that the inflammatory mechanisms associated with atherosclerosis and its complications can be modulated by anti-inflammatory molecules. A large amount of data also suggests that inflammation is a major component in the development and exacerbation of heart failure (HF), in a symbiotic relationship. In particular, recent evidence underlies peculiar aspects of the phenomenon: oxidative stress and autophagy; DAMPS and TLR-4 signaling activation; different macrophages lineage and the contribution of NLRP-3 inflammasome; adaptive immune system. A possible explanation that could unify the pathogenic mechanism of these different conditions is the rising evidence that increased bowel permeability may allow translation of gut microbioma product into the circulation. These findings clearly establish the role of inflammation as the great trigger for two of the major cardiovascular causes of death and morbidity. Further studies are needed, to better clarify the issue and to define more targeted approaches to reduce pathological inflammation while preserving the physiological one.

  14. Obesity, inflammation, and macrophages.

    Science.gov (United States)

    Subramanian, Vidya; Ferrante, Anthony W

    2009-01-01

    The World Health Organization estimates that since 1980 the prevalence of obesity has increased more than threefold throughout much of the world, and this increase is not limited to developed nations. Indeed, the incidence of obesity is increasing most rapidly among rapidly industrializing countries raising the spectre of a burgeoning epidemic in obesity-associated diseases, including diabetes, dyslipidemia, nonalcoholic fatty liver disease and atherosclerosis. Reducing the rates of obesity and its attendant complications will require both coordinated public health policy and a better understanding of the pathophysiology of obesity. Obesity is associated with low grade chronic inflammation, a common feature of many complications of obesity that appears to emanate in part from adipose tissue. In obese individuals and rodents adipose tissue macrophage accumulation is a critical component in the development of obesity-induced inflammation. The macrophages in adipose tissue are bone marrow-derived and their number is strongly correlated with bodyweight, body mass index and total body fat. The recruited macrophages in adipose tissue express high levels of inflammatory factors that contribute to systemic inflammation and insulin resistance. Interventions aimed at either reducing macrophage numbers or decreasing their inflammatory characteristics improves insulin sensitivity and decreases inflammation. Macrophage accumulation and adipose tissue inflammation are dynamic processes under the control of multiple mechanisms. Investigating the role of macrophages in adipose tissue biology and the mechanisms involved in their recruitment and activation in obesity will provide useful insights for developing therapeutic approaches to treating obesity-induced complications. Copyright (c) 2009 S. Karger AG, Basel.

  15. Changes in CREB and deltaFosB are associated with the behavioural sensitization induced by methylenedioxypyrovalerone.

    Science.gov (United States)

    Buenrostro-Jáuregui, Mario; Ciudad-Roberts, Andres; Moreno, Josep; Muñoz-Villegas, Patricia; López-Arnau, Raúl; Pubill, David; Escubedo, Elena; Camarasa, Jorge

    2016-07-01

    Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone which has recently emerged as a designer drug of abuse. The objective of this study was to investigate the locomotor sensitization induced by MDPV in adolescent mice, and associated neuroplastic changes in the nucleus accumbens and striatum through deltaFosB and CREB expression. Behavioural testing consisted of three phases: Phase I: conditioning regimen with MDPV (0.3 mg/kg/day for five days) or saline; Phase II: resting (11 days); Phase III: challenged with MDPV (0.3 mg/kg), cocaine (10 mg/kg) or saline on day 16 for both groups. Mice repeatedly exposed to MDPV increased locomotor activity by 165-200% following acute MDPV or cocaine administration after an 11-day resting period, showing a MDPV-induced sensitization to itself and to cocaine. An explanation for this phenomenon could be the common mechanism of action between these two psychostimulants. Furthermore, the MDPV challenge resulted in higher levels of phospho-CREB in MDPV-conditioned mice compared with MDPV-naive mice, probably due to an up-regulation of the cAMP pathway. Likewise, MDPV exposure induced a persistent increase in the striatal expression of deltaFosB; the priming dose of MDPV also produced a significant increase in the accumbal expression of this transcription factor. This study constitutes the first evidence that an exposure to a low dose of MDPV during adolescence induces behavioural sensitization and provides a neurobiological basis for a relationship between MDPV and cocaine. We hypothesize that, similar to cocaine, both CREB and deltaFosB play a role in the induction of this behavioural sensitization. © The Author(s) 2016.

  16. EXPERIMENTAL STUDIES ON INFLAMMATION

    Science.gov (United States)

    Wolf, Elizabeth Pauline

    1923-01-01

    1. None of the salts tested produce a marked inflammation in vivo in concentrations under 10 per cent. Potassium salts and the different citrates produced atypical inflammatory reactions in mice, but not in frogs. There was no true inflammation, however, characterized by blood vessel changes, migration of polymorphonuclear leucocytes and erythrocytes, and fluid exudation. 2. Synergistic action occurs when equal parts of strontium and magnesium salts are employed. There is a change in the appearance of the mesentery without a true inflammation, and this change does not occur with either salt alone. 3. Amino-acids and amines as a class do not produce inflammation, but histamine produces a marked inflammatory reaction in frogs and mice. 4. Tyramine does not cause an inflammatory reaction but has other marked effects; agglutination thrombi occur within the smaller blood vessels, both veins and arteries; in frogs there is a rapid clumping of the white blood cells followed by a true coagulation with strands of fibrin and entanglement of erythrocytes. This is very widespread and often kills the animal within an hour after injection. In mice it is the erythrocytes that clump and coagulation occurs very much later, usually at the end of 24 hours; still later there is complete absorption of the coagulated masses and the mesenteric circulation returns to normal. None of the mice died during the stage of clumping, and the clots never extended up the larger vessels as they did in the frogs. These effects are similar to the phenomena observed in the in vitro work, in which clumping of the cells appeared constantly. 5. Cantharidinum, histamine, and turpentine produced the most rapid and marked inflammation of any substances tried. These substances are all strongly positively chemotactic in vitro. The differences occurring when these substances are used in different species is a quantitative rather than a qualitative one, the body temperature being of some importance. Papain acted

  17. Osteoporosis, inflammation and ageing

    Directory of Open Access Journals (Sweden)

    Di Benedetto Maria

    2005-11-01

    Full Text Available Abstract Osteoporosis is a condition characterized by low bone mass and increased bone fragility, putting patients at risk of fractures, which are major causes of morbidity substantially in older people. Osteoporosis is currently attributed to various endocrine, metabolic and mechanical factors. However, emerging clinical and molecular evidence suggests that inflammation also exerts significant influence on bone turnover, inducing osteoporosis. Numerous proinflammatory cytokines have been implicated in the regulation of osteoblasts and osteoclasts, and a shift towards an activated immune profile has been hypothesized as important risk factor. Chronic inflammation and the immune system remodelling characteristic of ageing, as well as of other pathological conditions commonly associated with osteoporosis, may be determinant pathogenetic factors. The present article will review the current perspectives on the interaction between bone and immune system in the elderly, providing an interpretation of osteoporosis in the light of inflamm-ageing.

  18. Sinonasal inflammation in COPD

    DEFF Research Database (Denmark)

    Håkansson, Kåre; Konge, Lars; Thomsen, Sf

    2013-01-01

    In this review we demonstrate that patients with chronic obstructive pulmonary disease (COPD) frequently report sinonasal symptoms. Furthermore, we present evidence that smoking on its own can cause nasal disease, and that in COPD patients, nasal inflammation mimics that of the bronchi. All...... this evidence suggests that COPD related sinonasal disease does exist and that smoking on its own rather than systemic inflammation triggers the condition. However, COPD related sinonasal disease remains to be characterized in terms of symptoms and endoscopic findings. In addition, more studies are needed...... to quantify the negative impact of sinonasal symptoms on the quality of life in COPD patients....

  19. Obesity, Inflammation, and Cancer.

    Science.gov (United States)

    Deng, Tuo; Lyon, Christopher J; Bergin, Stephen; Caligiuri, Michael A; Hsueh, Willa A

    2016-05-23

    Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including cancer, and is increasingly recognized as a growing cause of preventable cancer risk. Chronic inflammation, a well-known mediator of cancer, is a central characteristic of obesity, leading to many of its complications, and obesity-induced inflammation confers additional cancer risk beyond obesity itself. Multiple mechanisms facilitate this strong association between cancer and obesity. Adipose tissue is an important endocrine organ, secreting several hormones, including leptin and adiponectin, and chemokines that can regulate tumor behavior, inflammation, and the tumor microenvironment. Excessive adipose expansion during obesity causes adipose dysfunction and inflammation to increase systemic levels of proinflammatory factors. Cells from adipose tissue, such as cancer-associated adipocytes and adipose-derived stem cells, enter the cancer microenvironment to enhance protumoral effects. Dysregulated metabolism that stems from obesity, including insulin resistance, hyperglycemia, and dyslipidemia, can further impact tumor growth and development. This review describes how adipose tissue becomes inflamed in obesity, summarizes ways these mechanisms impact cancer development, and discusses their role in four adipose-associated cancers that demonstrate elevated incidence or mortality in obesity.

  20. Inflammation, Immunity, and Hypertension.

    Science.gov (United States)

    Agita, Arisya; Alsagaff, M Thaha

    2017-04-01

    The immune system, inflammation and hypertension are related to each other. Innate and adaptive immunity system triggers an inflammatory process, in which blood pressure may increase, stimulating organ damage. Cells in innate immune system produce ROS, such as superoxide and hydrogen peroxide, which aimed at killing pathogens. Long-term inflammation process increases ROS production, causing oxidative stress which leads to endothelial dysfunction. Endothelial function is to regulate blood vessel tone and structure. When inflammation lasts, NO bioavailability decreases, disrupting its main function as vasodilator, so that blood vessels relaxation and vasodilatation are absent. Effector T cells and regulatory lymphocytes, part of the adaptive immune system, plays role in blood vessels constriction in hypertension. Signals from central nervous system and APC activates effector T lymphocyte differentiation and accelerate through Th-1 and Th-17 phenotypes. Th-1 and Th-17 effectors participate in inflammation which leads to increased blood pressure. One part of CD4+ is the regulatory T cells (Tregs) that suppress immune response activation as they produce immunosuppressive cytokines, such as TGF-β and IL-10. Adoptive transfer of Tregs cells can reduce oxidative stress in blood vessels, endothelial dysfunction, infiltration of aortic macrophages and T cells as well as proinflammatory cytokine levels in plasma circulation.

  1. Inflammation, Immunity, and Hypertension

    Directory of Open Access Journals (Sweden)

    Arisya Agita

    2017-04-01

    Full Text Available The immune system, inflammation and hypertension are related to each other. Innate and adaptive immunity system triggers an inflammatory process, in which blood pressure may increase, stimulating organ damage. Cells in innate immune system produce ROS, such as superoxide and hydrogen peroxide, which aimed at killing pathogens. Long-term inflammation process increases ROS production, causing oxidative stress which leads to endothelial dysfunction. Endothelial function is to regulate blood vessel tone and structure. When inflammation lasts, NO bioavailability decreases, disrupting its main function as vasodilator, so that blood vessels relaxation and vasodilatation are absent. Effector T cells and regulatory lymphocytes, part of the adaptive immune system, plays role in blood vessels constriction in hypertension. Signals from central nervous system and APC activates effector T lymphocyte differentiation and accelerate through Th-1 and Th-17 phenotypes. Th-1 and Th-17 effectors participate in inflammation which leads to increased blood pressure. One part of CD4+ is the regulatory T cells (Tregs that suppress immune response activation as they produce immunosuppressive cytokines, such as TGF-β and IL-10. Adoptive transfer of Tregs cells can reduce oxidative stress in blood vessels, endothelial dysfunction, infiltration of aortic macrophages and T cells as well as proinflammatory cytokine levels in plasma circulation.

  2. Idiopathic granulomatous orbital inflammation

    NARCIS (Netherlands)

    Mombaerts, I.; Schlingemann, R. O.; Goldschmeding, R.; Koornneef, L.

    1996-01-01

    PURPOSE: Granulomatous orbital inflammation may occur as an isolated condition of unknown origin. These idiopathic granulomatous lesions are believed to belong to the orbital pseudotumor group by some authors, whereas others consider them sarcoidosis limited to the orbit. The aim of this study is to

  3. Immunsystemet ved kronisk inflammation

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2008-01-01

    Innate and adaptive immunity has evolved as a defence against infections and as an important repair mechanism after physical injury. If elimination of microbes and healing is not achieved, or if the immune system is dysregulated, chronic inflammation ensues. Immune cells become engaged in prolonged...

  4. Cannabinoids, inflammation, and fibrosis.

    Science.gov (United States)

    Zurier, Robert B; Burstein, Sumner H

    2016-11-01

    Cannabinoids apparently act on inflammation through mechanisms different from those of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs). As a class, the cannabinoids are generally free from the adverse effects associated with NSAIDs. Their clinical development thus provides a new approach to treatment of diseases characterized by acute and chronic inflammation and fibrosis. A concise survey of the anti-inflammatory actions of the phytocannabinoids Δ9-tetrahydrocannabinol (THC), cannabidiol, cannabichromene, and cannabinol is presented. Mention is also made of the noncannabinoid plant components and pyrolysis products, followed by a discussion of 3 synthetic preparations-Cesamet (nabilone; Meda Pharmaceuticals, Somerset, NJ, USA), Marinol (dronabinol; THC; AbbVie, Inc., North Chicago, IL, USA), and Sativex (Cannabis extract; GW Pharmaceuticals, Cambridge United Kingdom)-that have anti-inflammatory effects. A fourth synthetic cannabinoid, ajulemic acid (AJA; CT-3; Resunab; Corbus Pharmaceuticals, Norwood, MA, USA), is discussed in greater detail because it represents the most recent advance in this area and is currently undergoing 3 phase 2 clinical trials by Corbus Pharmaceuticals. The endogenous cannabinoids, including the closely related lipoamino acids, are then discussed. The review concludes with a presentation of a possible mechanism for the anti-inflammatory and antifibrotic actions of these substances. Thus, several cannabinoids may be considered candidates for development as anti-inflammatory and antifibrotic agents. Of special interest is their possible use for treatment of chronic inflammation, a major unmet medical need.-Zurier, R. B., Burstein, S. H. Cannabinoids, inflammation, and fibrosis. © FASEB.

  5. Cytokines and intraocular inflammation

    NARCIS (Netherlands)

    Hoekzema, R.; Murray, P. I.; Kijlstra, A.

    1990-01-01

    Although new endogenous mediators of inflammatory and immune responses are reported almost on a monthly basis, the cytokines IL-1, TNF, and IL-6 have emerged as the primary regulators of local inflammation in man. In this paper, uveitogenic and other properties of these particular cytokines are

  6. inflammation and iron metabolism

    Directory of Open Access Journals (Sweden)

    A Dzedzej

    2016-08-01

    Full Text Available Following acute physical activity, blood hepcidin concentration appears to increase in response to exercise-induced inflammation, but the long-term impact of exercise on hepcidin remains unclear. Here we investigated changes in hepcidin and the inflammation marker interleukin-6 to evaluate professional basketball players’ response to a season of training and games. The analysis also included vitamin D (25(OHD3 assessment, owing to its anti-inflammatory effects. Blood samples were collected for 14 players and 10 control non-athletes prior to and after the 8-month competitive season. Athletes’ performance was assessed with the NBA efficiency score. At the baseline hepcidin correlated with blood ferritin (r=0.61; 90% CL ±0.31, but at the end of the season this correlation was absent. Compared with the control subjects, athletes experienced clear large increases in hepcidin (50%; 90% CI 15-96% and interleukin-6 (77%; 90% CI 35-131% and a clear small decrease in vitamin D (-12%; 90% CI -20 to -3% at the season completion. Correlations between change scores of these variables were unclear (r = -0.21 to 0.24, 90% CL ±0.5, but their uncertainty generally excluded strong relationships. Athletes were hence concluded to have experienced acute inflammation at the beginning but chronic inflammation at the end of the competitive season. At the same time, the moderate correlation between changes in vitamin D and players’ performance (r=0.43 was suggestive of its beneficial influence. Maintaining the appropriative concentration of vitamin D is thus necessary for basketball players’ performance and efficiency. The assessment of hepcidin has proven to be useful in diagnosing inflammation in response to chronic exercise.

  7. Gut Microbiota and Inflammation

    Directory of Open Access Journals (Sweden)

    Goran Molin

    2011-06-01

    Full Text Available Systemic and local inflammation in relation to the resident microbiota of the human gastro-intestinal (GI tract and administration of probiotics are the main themes of the present review. The dominating taxa of the human GI tract and their potential for aggravating or suppressing inflammation are described. The review focuses on human trials with probiotics and does not include in vitro studies and animal experimental models. The applications of probiotics considered are systemic immune-modulation, the metabolic syndrome, liver injury, inflammatory bowel disease, colorectal cancer and radiation-induced enteritis. When the major genomic differences between different types of probiotics are taken into account, it is to be expected that the human body can respond differently to the different species and strains of probiotics. This fact is often neglected in discussions of the outcome of clinical trials with probiotics.

  8. Nanoparticles and Inflammation

    Directory of Open Access Journals (Sweden)

    Ross Stevenson

    2011-01-01

    Full Text Available The development of nanoscale molecular probes capable of diagnosis, characterization, and clinical treatment of disease is leading to a new generation of imaging technologies. Such probes are particularly relevant to inflammation, where the detection of subclinical, early disease states could facilitate speedier detection that could yield enhanced, tailored therapies. Nanoparticles offer robust platforms capable of sensitive detection, and early research has indicated their suitability for the detection of vascular activation and cellular recruitment at subclinical levels. This suggests that nanoparticle techniques may provide excellent biomarkers for the diagnosis and progression of inflammatory diseases with magnetic resonance imaging (MRI, fluorescent quantum dots (QDs, and surface enhanced Raman scattering (SERS probes being just some of the new methodologies employed. Development of these techniques could lead to a range of sensitive probes capable of ultrasensitive, localized detection of inflammation. This article will discuss the merits of each approach, with a general overview to their applicability in inflammatory diseases.

  9. Midkine in Inflammation

    Directory of Open Access Journals (Sweden)

    Ludwig T. Weckbach

    2011-01-01

    Full Text Available The 13 kDa heparin-binding growth factor midkine (MK was originally identified as a molecule involved in the orchestration of embryonic development. Recent studies provided evidence for a new role of MK in acute and chronic inflammatory processes. Accordingly, several inflammatory diseases including nephritis, arthritis, atherosclerosis, colitis, and autoimmune encephalitis have been shown to be alleviated in the absence of MK in animal models. Reduced leukocyte recruitment to the sites of inflammation was found to be one important mechanism attenuating chronic inflammation when MK was absent. Furthermore, MK was found to modulate expression of proinflammatory cytokines and the expansion of regulatory T-cells. Here, we review the current understanding of the role of MK in different inflammatory disorders and summarize the knowledge of MK biology.

  10. Inflammation in Epileptic Encephalopathies.

    Science.gov (United States)

    Shandra, Oleksii; Moshé, Solomon L; Galanopoulou, Aristea S

    2017-01-01

    West syndrome (WS) is an infantile epileptic encephalopathy that manifests with infantile spasms (IS), hypsarrhythmia (in ~60% of infants), and poor neurodevelopmental outcomes. The etiologies of WS can be structural-metabolic pathologies (~60%), genetic (12%-15%), or of unknown origin. The current treatment options include hormonal treatment (adrenocorticotropic hormone and high-dose steroids) and the GABA aminotransferase inhibitor vigabatrin, while ketogenic diet can be given as add-on treatment in refractory IS. There is a need to identify new therapeutic targets and more effective treatments for WS. Theories about the role of inflammatory pathways in the pathogenesis and treatment of WS have emerged, being supported by both clinical and preclinical data from animal models of WS. Ongoing advances in genetics have revealed numerous genes involved in the pathogenesis of WS, including genes directly or indirectly involved in inflammation. Inflammatory pathways also interact with other signaling pathways implicated in WS, such as the neuroendocrine pathway. Furthermore, seizures may also activate proinflammatory pathways raising the possibility that inflammation can be a consequence of seizures and epileptogenic processes. With this targeted review, we plan to discuss the evidence pro and against the following key questions. Does activation of inflammatory pathways in the brain cause epilepsy in WS and does it contribute to the associated comorbidities and progression? Can activation of certain inflammatory pathways be a compensatory or protective event? Are there interactions between inflammation and the neuroendocrine system that contribute to the pathogenesis of WS? Does activation of brain inflammatory signaling pathways contribute to the transition of WS to Lennox-Gastaut syndrome? Are there any lead candidates or unexplored targets for future therapy development for WS targeting inflammation? © 2017 Elsevier Inc. All rights reserved.

  11. Inflammation in Diabetic Nephropathy

    Science.gov (United States)

    Lim, Andy K. H.; Tesch, Gregory H.

    2012-01-01

    Diabetic nephropathy is the leading cause of end-stage kidney disease worldwide but current treatments remain suboptimal. This review examines the evidence for inflammation in the development and progression of diabetic nephropathy in both experimental and human diabetes, and provides an update on recent novel experimental approaches targeting inflammation and the lessons we have learned from these approaches. We highlight the important role of inflammatory cells in the kidney, particularly infiltrating macrophages, T-lymphocytes and the subpopulation of regulatory T cells. The possible link between immune deposition and diabetic nephropathy is explored, along with the recently described immune complexes of anti-oxidized low-density lipoproteins. We also briefly discuss some of the major inflammatory cytokines involved in the pathogenesis of diabetic nephropathy, including the role of adipokines. Lastly, we present the latest data on the pathogenic role of the stress-activated protein kinases in diabetic nephropathy, from studies on the p38 mitogen activated protein kinase and the c-Jun amino terminal kinase cell signalling pathways. The genetic and pharmacological approaches which reduce inflammation in diabetic nephropathy have not only enhanced our understanding of the pathophysiology of the disease but shown promise as potential therapeutic strategies. PMID:22969168

  12. Inflammation in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Andy K. H. Lim

    2012-01-01

    Full Text Available Diabetic nephropathy is the leading cause of end-stage kidney disease worldwide but current treatments remain suboptimal. This review examines the evidence for inflammation in the development and progression of diabetic nephropathy in both experimental and human diabetes, and provides an update on recent novel experimental approaches targeting inflammation and the lessons we have learned from these approaches. We highlight the important role of inflammatory cells in the kidney, particularly infiltrating macrophages, T-lymphocytes and the subpopulation of regulatory T cells. The possible link between immune deposition and diabetic nephropathy is explored, along with the recently described immune complexes of anti-oxidized low-density lipoproteins. We also briefly discuss some of the major inflammatory cytokines involved in the pathogenesis of diabetic nephropathy, including the role of adipokines. Lastly, we present the latest data on the pathogenic role of the stress-activated protein kinases in diabetic nephropathy, from studies on the p38 mitogen activated protein kinase and the c-Jun amino terminal kinase cell signalling pathways. The genetic and pharmacological approaches which reduce inflammation in diabetic nephropathy have not only enhanced our understanding of the pathophysiology of the disease but shown promise as potential therapeutic strategies.

  13. Stress increases periodontal inflammation

    Science.gov (United States)

    RIVERA, CÉSAR; MONSALVE, FRANCISCO; SUAZO, IVÁN; BECERRA, JAVIERA

    2012-01-01

    This study aimed to examine the effect of chronic restraint stress (RS) on the severity of experimental periodontal disease in rats. A total of 32 male Sprague Dawley (SD) rats were divided into four groups: i) Rats receiving two treatment regimens, chronic stress induced by movement restriction in acrylic cylinders for 1–1.5 h daily and induction of experimental periodontal disease, using a nylon ligature which was placed around the first left mandibular molars (n=8); ii) induction of periodontal disease, without RS (n=8); iii) RS (n=8) and iv) control (n=8). After 15 days, blood samples were obtained, and blood glucose levels and the corticosterone concentration were measured as stress markers. The severity of periodontal disease was analyzed according to the level of gingival and bone inflammation, leading to compromise of the teeth involved. Chronic stress was induced with movement restriction (P≤0.05, Mann-Whitney U-test) and increased the severity (P≤0.05, Mann-Whitney U-test) of experimental perio dontal disease in rats, according to the level of gingival and bone inflammation around the first left mandibular molars. The results of the present study showed that RS modulates periodontal inflammation and that the rat model described herein is suitable for investigating the association between stress and periodontal disease. PMID:23226743

  14. Cytokines and intestinal inflammation.

    Science.gov (United States)

    Bamias, Giorgos; Cominelli, Fabio

    2016-11-01

    Cytokines of the intestinal microenvironment largely dictate immunological responses after mucosal insults and the dominance of homeostatic or proinflammatory pathways. This review presents important recent studies on the role of specific cytokines in the pathogenesis of intestinal inflammation. The particular mucosal effects of cytokines depend on their inherent properties but also the cellular origin, type of stimulatory antigens, intermolecular interactions, and the particular immunological milieu. Novel cytokines of the interleukin-1 (IL-1) family, including IL-33 and IL-36, have dominant roles in mucosal immunity, whereas more established ones such as IL-18 are constantly enriched with unique properties. Th17 cells are important mucosal constituents, although their profound plasticity, makes the specific set of cytokines they secrete more important than their mere numbers. Finally, various cytokines, such as tumor necrosis factor-α, IL-6, tumor necrosis factor-like cytokine 1A, and death receptor, 3 demonstrate dichotomous roles with mucosa-protective function in acute injury but proinflammatory effects during chronic inflammation. The role of cytokines in mucosal health and disease is increasingly revealed. Such information not only will advance our understanding of the pathogenesis of gut inflammation, but also set the background for development of reliable diagnostic and prognostic biomarkers and cytokine-specific therapies.

  15. Inflammation in Chronic Wounds.

    Science.gov (United States)

    Zhao, Ruilong; Liang, Helena; Clarke, Elizabeth; Jackson, Christopher; Xue, Meilang

    2016-12-11

    Non-healing chronic wounds present a major biological, psychological, social, and financial burden on both individual patients and the broader health system. Pathologically extensive inflammation plays a major role in the disruption of the normal healing cascade. The causes of chronic wounds (venous, arterial, pressure, and diabetic ulcers) can be examined through a juxtaposition of normal healing and the rogue inflammatory response created by the common components within chronic wounds (ageing, hypoxia, ischaemia-reperfusion injury, and bacterial colonisation). Wound bed care through debridement, dressings, and antibiotics currently form the basic mode of treatment. Despite recent setbacks, pharmaceutical adjuncts form an interesting area of research.

  16. Inflammation in Diabetic Retinopathy

    Science.gov (United States)

    Tang, Johnny; Kern, Timothy S.

    2012-01-01

    Diabetes causes a number of metabolic and physiologic abnormalities in the retina, but which of these abnormalities contribute to recognized features of diabetic retinopathy (DR) is less clear. Many of the molecular and physiologic abnormalities that have been found to develop in the retina in diabetes are consistent with inflammation. Moreover, a number of anti-inflammatory therapies have been found to significantly inhibit development of different aspects of DR in animal models. Herein, we review the inflammatory mediators and their relationship to early and late DR, and discuss the potential of anti-inflammatory approaches to inhibit development of different stages of the retinopathy. We focus primarily on information derived from in vivo studies, supplementing with information from in vitro studies were important. PMID:21635964

  17. Microbiota, inflammation and obesity.

    Science.gov (United States)

    Sanz, Yolanda; Moya-Pérez, Angela

    2014-01-01

    Interactions between metabolism and immunity play a pivotal role in the development of obesity-associated chronic co-morbidities. Obesity involves impairment of immune function affecting both the innate and adaptive immune system. This leads to increased risk of infections as well as chronic low-grade inflammation, which in turn causes metabolic dysfunction (e.g. insulin resistance) and chronic disease (e.g. type-2 diabetes). Gut microbiota has emerged as one of the key factors regulating early events triggering inflammation associated with obesity and metabolic dysfunction. This effect seems to be related to diet- and obesity-associated changes in gut microbiota composition and to increased translocation of immunogenic bacterial products, which activate innate and adaptive immunity in the gut and beyond, contributing to an increase in inflammatory tone. Innate immune receptors, like Toll-like receptors (TLRs), are known to be up-regulated in the tissue affected by most inflammatory disorders and activated by both specific microbial components and dietary lipids. This triggers several signaling transduction pathways (e.g. JNK and IKKβ/NF-κB), leading to inflammatory cytokine and chemokine (TNF-α, IL-1, MCP1) production and to inflammatory cell recruitment, causing insulin resistance. T-cell differentiation into effector inflammatory or regulatory T cells also depends on the type of TLR activated and on cytokine production, which in turn depends upon gut microbiota-diet interactions. Here, we update and discuss our current understanding of how gut microbiota could contribute to defining whole-body metabolism by influencing diverse components of the innate and adaptive immune system, both locally and systemically.

  18. Chronic inflammation and cardiovascular risk

    African Journals Online (AJOL)

    Review: Chronic inflammation and cardiovascular risk. 18. Vol 52 No 1. SA Fam Pract 2010. SA Fam Pract 2010;52(1): 18. Much evidence points towards inflammation as a key regulatory process linking cardiovascular risk factors for atherosclerosis and its complications to an altered arterial biology.1 Systemic inflammatory ...

  19. Inflammation markers in essential hypertension.

    Science.gov (United States)

    Tsounis, Dimitrios; Bouras, Georgios; Giannopoulos, Georgios; Papadimitriou, Charalampos; Alexopoulos, Dimitrios; Deftereos, Spyridon

    2014-01-01

    Essential hypertension is a common health disorder with uncertain etiology and unclear pathophysiology. There is evidence that various systems interact in uncertain ways and mechanisms to cause hypertension. It is also well known that inflammation is a key feature in the initiation, progression and clinical implication of several cardiovascular diseases. Recently, it has become evident that the immune system and inflammatory response are also essential in the pathogenesis of hypertension. Many inflammation markers such as CRP, cytokines, and adhesion molecules have been found elevated in hypertensive patients supporting the role of inflammation in the pathogenesis of hypertension. Also, in normotensive individuals, these markers have been associated with the risk of developing hypertension, whereas in hypertensive patients they have been associated with target organ damage as well as with the risk for future cardiovascular events. Thus, understanding the role of inflammation in hypertension provides new insights for novel therapeutic approaches, targeting inflammation for the treatment of hypertension and its complications.

  20. Anemia of Inflammation and Chronic Disease

    Science.gov (United States)

    ... Chronic Disease Aplastic Anemia & Myelodysplastic Syndromes Anemia of Inflammation & Chronic Disease What is anemia? Anemia is a ... other organs to fail. What is anemia of inflammation and chronic disease (AI/ACD)? Anemia of inflammation ...

  1. Metabolic regulation of inflammation.

    Science.gov (United States)

    Gaber, Timo; Strehl, Cindy; Buttgereit, Frank

    2017-05-01

    Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions. In the past 5 years, it has become clear that cellular metabolism affects immune cell function and differentiation, and that disease-specific metabolic configurations might provide an explanation for the dysfunctional immune responses seen in rheumatic diseases. This Review outlines the metabolic challenges faced by immune cells in states of homeostasis and inflammation, as well as the variety of metabolic configurations utilized by immune cells during differentiation and activation. Changes in cellular metabolism that contribute towards the dysfunctional immune responses seen in rheumatic diseases are also briefly discussed.

  2. Leptospira and Inflammation

    Directory of Open Access Journals (Sweden)

    C. F. Gonçalves-de-Albuquerque

    2012-01-01

    Full Text Available Leptospirosis is an important zoonosis and has a worldwide impact on public health. This paper will discuss both the role of immunogenic and pathogenic molecules during leptospirosis infection and possible new targets for immunotherapy against leptospira components. Leptospira, possess a wide variety of mechanisms that allow them to evade the host immune system and cause infection. Many molecules contribute to the ability of Leptospira to adhere, invade, and colonize. The recent sequencing of the Leptospira genome has increased our knowledge about this pathogen. Although the virulence factors, molecular targets, mechanisms of inflammation, and signaling pathways triggered by leptospiral antigens have been studied, some questions are still unanswered. Toll-like receptors (TLRs are the primary sensors of invading pathogens. TLRs recognize conserved microbial pattern molecules and activate signaling pathways that are pivotal to innate and adaptive immune responses. Recently, a new molecular target has emerged—the Na/K-ATPase—which may contribute to inflammatory and metabolic alteration in this syndrome. Na/K-ATPase is a target for specific fatty acids of host origin and for bacterial components such as the glycolipoprotein fraction (GLP that may lead to inflammasome activation. We propose that in addition to TLRs, Na/K-ATPase may play a role in the innate response to leptospirosis infection.

  3. Nutrition, inflammation, and cognitive function.

    Science.gov (United States)

    Wärnberg, Julia; Gomez-Martinez, Sonia; Romeo, Javier; Díaz, Ligia-Esperanza; Marcos, Ascensión

    2009-02-01

    Inflammation, particularly low-grade chronic inflammation, appears to affect several brain functions, from early brain development to the development of neurodegenerative disorders and perhaps some psychiatric diseases. On the other hand, nutrition and dietary components and patterns have a plethora of anti- and pro-inflammatory effects that could be linked to cognitive function. Even a modest effect of nutrition on cognitive decline could have significant implications for public health. This paper summarizes the available evidence regarding inflammation as a key mechanism in cognitive function and nutritional pro- or anti-inflammatory effects with the purpose of linking the apparent disparate disciplines of nutrition, immunity, and neurology.

  4. Inflammation-related cancer or cancer-related inflammation

    OpenAIRE

    T.G, Shrihari

    2018-01-01

    Inflammationis the body’s defensive action against various stimuli such as physical orchemical or infectious agents. Acute inflammation and their mediators help intissue repair and healing. If the inflammation aggravates chronically,non-resolved, dysregulated immune system, results release of various inflammatorymediators such as free radicals (ROS and RNS), cytokines, chemokines, growthfactors and proteolytic enzymes produced by innate and adaptive immune cellsactivate transcriptional factor...

  5. Apoptosis and inflammation

    Directory of Open Access Journals (Sweden)

    C. Haanen

    1995-01-01

    Full Text Available During the last few decades it has been recognized that cell death is not the consequence of accidental injury, but is the expression of a cell suicide programme. Kerr et al. (1972 introduced the term apoptosis. This form of cell death is under the influence of hormones, growth factors and cytokines, which depending upon the receptors present on the target cells, may activate a genetically controlled cell elimination process. During apoptosis the cell membrane remains intact and the cell breaks into apoptotic bodies, which are phagocytosed. Apoptosis, in contrast to necrosis, is not harmful to the host and does not induce any inflammatory reaction. The principal event that leads to inflammatory disease is cell damage, induced by chemical/physical injury, anoxia or starvation. Cell damage means leakage of cell contents into the adjacent tissues, resulting in the capillary transmigration of granulocytes to the injured tissue. The accumulation of neutrophils and release of enzymes and oxygen radicals enhances the inflammatory reaction. Until now there has been little research into the factors controlling the accumulation and the tissue load of granulocytes and their histotoxic products in inflammatory processes. Neutrophil apoptosis may represent an important event in the control of intlamtnation. It has been assumed that granulocytes disintegrate to apoptotic bodies before their fragments are removed by local macrophages. Removal of neutrophils from the inflammatory site without release of granule contents is of paramount importance for cessation of inflammation. In conclusion, apoptotic cell death plays an important role in inflammatory processes and in the resolution of inflammatory reactions. The facts known at present should stimulate further research into the role of neutrophil, eosinophil and macrophage apoptosis in inflammatory diseases.

  6. Lamin in inflammation and aging.

    Science.gov (United States)

    Tran, Joseph R; Chen, Haiyang; Zheng, Xiaobin; Zheng, Yixian

    2016-06-01

    Aging is characterized by a progressive loss of tissue function and an increased susceptibility to injury and disease. Many age-associated pathologies manifest an inflammatory component, and this has led to the speculation that aging is at least in part caused by some form of inflammation. However, whether or not inflammation is truly a cause of aging, or is a consequence of the aging process is unknown. Recent work using Drosophila has uncovered a mechanism where the progressive loss of lamin-B in the fat body upon aging triggers systemic inflammation. This inflammatory response perturbs the local immune response of the neighboring gut tissue and leads to hyperplasia. Here, we will discuss the literature connecting lamins to aging and inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Alveolar inflammation in cystic fibrosis

    DEFF Research Database (Denmark)

    Ulrich, Martina; Worlitzsch, Dieter; Viglio, Simona

    2010-01-01

    BACKGROUND: In infected lungs of the cystic fibrosis (CF) patients, opportunistic pathogens and mutated cystic fibrosis transmembrane conductance regulator protein (CFTR) contribute to chronic airway inflammation that is characterized by neutrophil/macrophage infiltration, cytokine release and ce...

  8. Role of platelets in inflammation

    Directory of Open Access Journals (Sweden)

    Kadir Serkan Yalçın

    2012-09-01

    Full Text Available Inflammation, which is extremely useful process for humanbody is the response of living vascular tissues topathological phenomena that removes the pathogens andinitiates the healing procedure. Microorganisms, physicaltrauma, chemical, mechanical, irradiation, or thermal injury,ischemia and immune reactions are most commoncauses of this exceptionally important event for humanbody. Platelets are non-nucleated cells in blood that producedin bone marrow as derived from megakaryocytes.Apart from stop bleeding and achieving hemostasis thereare incredibly important roles of platelets in inflammation.Platelets contain important mediators for inflammationlike neutrophils or macrophages and can alter the courseof mechanism. In this article changing platelet function ininflammation and the effect of these functions to the processof inflammation will be discussed.Key words: Platelet, inflammation, cytokines

  9. Close Relationships, Inflammation, and Health

    OpenAIRE

    Kiecolt-Glaser, Janice K.; Gouin, Jean-Philippe; Hantsoo, Liisa

    2009-01-01

    KIECOLT-GLASER, J.K., J-P. Gouin, and L. Hantsoo, Close Relationships, Inflammation, and Health. NEUROSCI BIOBEHAV REV XX(X) XXX-XXX, 2009.- Different aspects of personal relationships including social integration, social support, and social conflict have been related to inflammation. This article summarizes evidence linking the quality and quantity of relationships with gene expression, intracellular signaling mechanisms, and inflammatory biomarkers, and highlights the biological and psychol...

  10. Lamin in inflammation and aging

    OpenAIRE

    Tran, Joseph R.; Chen, Haiyang; Zheng, Xiaobin; Zheng, Yixian

    2016-01-01

    Aging is characterized by a progressive loss of tissue function and an increased susceptibility to injury and disease. Many age-associated pathologies manifest an inflammatory component, and this has led to the speculation that aging is at least in part caused by some form of inflammation. However, whether or not inflammation is truly a cause of aging, or is a consequence of the aging process is unknown. Recent work using Drosophila has uncovered a mechanism where the progressive loss of lami...

  11. Crystalline silica-induced inflammation

    OpenAIRE

    2010-01-01

    M. Tech. The persistent presence of neutrophils is associated with a wide range of inflammatory diseases. Resolution of inflammation in these diseases is also associated with the ingestion of apoptotic neutrophils by macrophages. Inflammation and apoptosis of inflammatory cells are common known features observed in the lung following exposure to crystalline silica. What is not known is how well these apoptotic cells are cleared by macrophages in the presence of crystalline silica? To inves...

  12. FOXM1 promotes allergen-induced goblet cell metaplasia and pulmonary inflammation.

    Science.gov (United States)

    Ren, Xiaomeng; Shah, Tushar A; Ustiyan, Vladimir; Zhang, Yufang; Shinn, John; Chen, Gang; Whitsett, Jeffrey A; Kalin, Tanya V; Kalinichenko, Vladimir V

    2013-01-01

    Chronic airway disorders, including chronic obstructive pulmonary disease (COPD), cystic fibrosis, and asthma, are associated with persistent pulmonary inflammation and goblet cell metaplasia and contribute to significant morbidity and mortality worldwide. While the molecular pathogenesis of these disorders is actively studied, little is known regarding the transcriptional control of goblet cell differentiation and mucus hyperproduction. Herein, we demonstrated that pulmonary allergen sensitization induces expression of FOXM1 transcription factor in airway epithelial and inflammatory cells. Conditional deletion of the Foxm1 gene from either airway epithelium or myeloid inflammatory cells decreased goblet cell metaplasia, reduced lung inflammation, and decreased airway resistance in response to house dust mite allergen (HDM). FOXM1 induced goblet cell metaplasia and Muc5AC expression through the transcriptional activation of Spdef. FOXM1 deletion reduced expression of CCL11, CCL24, and the chemokine receptors CCR2 and CX3CR1, resulting in decreased recruitment of eosinophils and macrophages to the lung. Deletion of FOXM1 from dendritic cells impaired the uptake of HDM antigens and decreased cell surface expression of major histocompatibility complex II (MHC II) and costimulatory molecule CD86, decreasing production of Th2 cytokines by activated T cells. Finally, pharmacological inhibition of FOXM1 by ARF peptide prevented HDM-mediated pulmonary responses. FOXM1 regulates genes critical for allergen-induced lung inflammation and goblet cell metaplasia.

  13. EXPERIMENTAL STUDIES ON INFLAMMATION : II. EXPERIMENTAL CHEMICAL INFLAMMATION IN VIVO.

    Science.gov (United States)

    Wolf, E P

    1923-03-31

    1. None of the salts tested produce a marked inflammation in vivo in concentrations under 10 per cent. Potassium salts and the different citrates produced atypical inflammatory reactions in mice, but not in frogs. There was no true inflammation, however, characterized by blood vessel changes, migration of polymorphonuclear leucocytes and erythrocytes, and fluid exudation. 2. Synergistic action occurs when equal parts of strontium and magnesium salts are employed. There is a change in the appearance of the mesentery without a true inflammation, and this change does not occur with either salt alone. 3. Amino-acids and amines as a class do not produce inflammation, but histamine produces a marked inflammatory reaction in frogs and mice. 4. Tyramine does not cause an inflammatory reaction but has other marked effects; agglutination thrombi occur within the smaller blood vessels, both veins and arteries; in frogs there is a rapid clumping of the white blood cells followed by a true coagulation with strands of fibrin and entanglement of erythrocytes. This is very widespread and often kills the animal within an hour after injection. In mice it is the erythrocytes that clump and coagulation occurs very much later, usually at the end of 24 hours; still later there is complete absorption of the coagulated masses and the mesenteric circulation returns to normal. None of the mice died during the stage of clumping, and the clots never extended up the larger vessels as they did in the frogs. These effects are similar to the phenomena observed in the in vitro work, in which clumping of the cells appeared constantly. 5. Cantharidinum, histamine, and turpentine produced the most rapid and marked inflammation of any substances tried. These substances are all strongly positively chemotactic in vitro. The differences occurring when these substances are used in different species is a quantitative rather than a qualitative one, the body temperature being of some importance. Papain acted

  14. Bioactive Egg Components and Inflammation

    Directory of Open Access Journals (Sweden)

    Catherine J. Andersen

    2015-09-01

    Full Text Available Inflammation is a normal acute response of the immune system to pathogens and tissue injury. However, chronic inflammation is known to play a significant role in the pathophysiology of numerous chronic diseases, such as cardiovascular disease, type 2 diabetes mellitus, and cancer. Thus, the impact of dietary factors on inflammation may provide key insight into mitigating chronic disease risk. Eggs are recognized as a functional food that contain a variety of bioactive compounds that can influence pro- and anti-inflammatory pathways. Interestingly, the effects of egg consumption on inflammation varies across different populations, including those that are classified as healthy, overweight, metabolic syndrome, and type 2 diabetic. The following review will discuss the pro- and anti-inflammatory properties of egg components, with a focus on egg phospholipids, cholesterol, the carotenoids lutein and zeaxanthin, and bioactive proteins. The effects of egg consumption of inflammation across human populations will additionally be presented. Together, these findings have implications for population-specific dietary recommendations and chronic disease risk.

  15. Endogenous Receptor Agonists: Resolving Inflammation

    Directory of Open Access Journals (Sweden)

    Gerhard Bannenberg

    2007-01-01

    Full Text Available Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution.

  16. Sirtuins Link Inflammation and Metabolism

    Directory of Open Access Journals (Sweden)

    Vidula T. Vachharajani

    2016-01-01

    Full Text Available Sirtuins (SIRT, first discovered in yeast as NAD+ dependent epigenetic and metabolic regulators, have comparable activities in human physiology and disease. Mounting evidence supports that the seven-member mammalian sirtuin family (SIRT1–7 guard homeostasis by sensing bioenergy needs and responding by making alterations in the cell nutrients. Sirtuins play a critical role in restoring homeostasis during stress responses. Inflammation is designed to “defend and mend” against the invading organisms. Emerging evidence supports that metabolism and bioenergy reprogramming direct the sequential course of inflammation; failure of homeostasis retrieval results in many chronic and acute inflammatory diseases. Anabolic glycolysis quickly induced (compared to oxidative phosphorylation for ROS and ATP generation is needed for immune activation to “defend” against invading microorganisms. Lipolysis/fatty acid oxidation, essential for cellular protection/hibernation and cell survival in order to “mend,” leads to immune repression. Acute/chronic inflammations are linked to altered glycolysis and fatty acid oxidation, at least in part, by NAD+ dependent function of sirtuins. Therapeutically targeting sirtuins may provide a new class of inflammation and immune regulators. This review discusses how sirtuins integrate metabolism, bioenergetics, and immunity during inflammation and how sirtuin-directed treatment improves outcome in chronic inflammatory diseases and in the extreme stress response of sepsis.

  17. Chronic Inflammation in cancer development

    Directory of Open Access Journals (Sweden)

    Gabriele eMulthoff

    2012-01-01

    Full Text Available Chronic inflammatory mediators exert pleiotropic effects in the development of cancer. On the one hand, inflammation favors carcinogenesis, malignant transformation, tumor growth, invasion and metastatic spread; on the other hand inflammation can stimulate immune effector mechanisms that might limit tumor growth. The link between cancer and inflammation depends on intrinsic and extrinsic pathways. Both pathways result in the activation of transcription factors such as NF-B, STAT-3, and HIF-1 and in accumulation of tumorigenic factors in tumor and microenvironment. STAT-3 and NF-B interact at multiple levels and thereby boost tumor-associated inflammation which can suppress anti-tumor immune responses. These factors also promote tumor growth, progression and metastatic spread. IL-1, IL-6, TNF and PGHS-2 are key mediators of an inflammatory milieu by modulating the expression of tumor-promoting factors. In this review we concentrate on the crucial role of pro-inflammatory mediators in inflammation-driven carcinogenesis and outline molecular mechanisms of IL-1 signaling in tumors. In addition, we elucidate the dual roles of stress proteins as danger signals in the development of anti-cancer immunity and anti-apoptotic functions.

  18. Granulomatous inflammation in Acanthamoeba sclerokeratitis

    Directory of Open Access Journals (Sweden)

    Samrat Chatterjee

    2013-01-01

    Full Text Available This report describes the histopathological findings in a patient with Acanthamoeba sclerokeratitis (ASK. A 58-year-old patient with ASK underwent enucleation and sections of the cornea and sclera were subjected to histopathology and immunohistochemistry with monoclonal mouse antihuman antibodies against T cell CD3 and B cell CD20 antigens. Hematoxylin and Eosin stained sections of the cornea revealed epithelial ulceration, Bowman′s membrane destruction, stromal vascularization, infiltration with lymphocytes, plasma cells, and granulomatous inflammation with multinucleated giant cells (MNGC. The areas of scleritis showed complete disruption of sclera collagen, necrosis and infiltration with neutrophils, macrophages, lymphocytes, and granulomatous inflammation with MNGC. No cyst or trophozoites of Acanthamoeba were seen in the cornea or sclera. Immunophenotyping revealed that the population of lymphocytes was predominantly of T cells. Granulomatous inflammation in ASK is probably responsible for the continuance and progression of the scleritis and management protocols should include immunosuppressive agents alongside amoebicidal drugs.

  19. Effect of ASF (a Compound of Traditional Chinese Medicine) on Behavioral Sensitization Induced by Ethanol and Conditioned Place Preference in Mice.

    Science.gov (United States)

    Wen, Da-Chao; Li, Yi-Bei; Hu, Xiao-Yu; Lin, Wu; Jia, Ling-Yan; Zhong, Sen

    2014-01-01

    ASF composed by semen and epimedium herbal is a traditional plant compound that is widely used in the treatment of insomnia. Studies have shown that saponins and flavonoids contained in semen can significantly decrease the content of excitatory neurotransmitter Glu in mice. And the total flavone of YinYangHuo can increase the release of GABA in the anterior periventricular system of rat and increase the affinity of GABA for the receptors GABAA. It can be inferred that their synergism may have effect on the neurotransmitter that causes behavioral sensitization and conditioned place preference in experimental animals and affects their drinking behaviors, which is the starting point of this research. The present study found that ASF can inhibit development and expression of behavioral sensitization induced by ethanol and the development of CPP in mice. We demonstrate the inhibition of ASF on behavioral sensitization partly due to its effect on the mesolimbic neurotransmitter system, including decreasing level of DA and Glu and increasing the content of GABA. It suggested that the ASF may have pharmacological effects in the treatment of alcohol addiction.

  20. Systemic Treatment of Vitreous Inflammation

    Directory of Open Access Journals (Sweden)

    John B. Christoforidis

    2012-01-01

    Full Text Available Non infectious vitreous inflammation is often vision threatening and can be associated with potentially life-threatening systemic conditions. Treatment is often challenging as it involves systemic medications that can be associated with adverse effects. The classes of drugs are ever expanding and include corticosteroids, antimetabolites, alkylating agents, T-cell and calcineurin agents, biologic agents, and interferons. Each class of systemic therapy for non-infectious vitreous inflammation is reviewed. We discuss the mechanisms of action, usual clinical dosages, the specific conditions that are treated, the adverse effects, and usual course of treatment for each class of therapy.

  1. Preeclampsia, Hypoxia, Thrombosis, and Inflammation

    Directory of Open Access Journals (Sweden)

    Amir A. Shamshirsaz

    2012-01-01

    Full Text Available Reductions in uteroplacental flow initiate a cascade of molecular effects leading to hypoxia, thrombosis, inflammation, and endothelial cell dysfunction resulting in untoward pregnancy outcomes. In this review, we detail these effects and their relationship to preeclampsia (PE and intrauterine growth restriction (IUGR.

  2. Genetic models for CNS inflammation

    DEFF Research Database (Denmark)

    Owens, T; Wekerle, H; Antel, J

    2001-01-01

    The use of transgenic technology to over-express or prevent expression of genes encoding molecules related to inflammation has allowed direct examination of their role in experimental disease. This article reviews transgenic and knockout models of CNS demyelinating disease, focusing primarily...

  3. Smoke producing and inflammable materials

    NARCIS (Netherlands)

    Wilms EB; van Xanten NHW; Meulenbelt J

    1990-01-01

    On behalf of the AMGB (Afdeling Militair Geneeskundig Beleid) toxicological reviews have been made about several smoke producing and inflammable materials. The reviews have been made after a literature search and are meant to complete or to replace the concerning chapters in the NATO handbook on

  4. Chronic inflammation and cardiovascular risk

    African Journals Online (AJOL)

    treated patients who not only achieved LDL-cholesterol levels below 1.8 mmol/L but who also achieved CRP levels below. 2 mg/L.2. The Jupiter trial tested this hypothesis prospectively. Maximum treatment benefit occurred with reduction of both LDL-cholesterol and CRP levels.3 Is there a future of targeting inflammation in.

  5. Purinergic Receptors in Ocular Inflammation

    Directory of Open Access Journals (Sweden)

    Ana Guzman-Aranguez

    2014-01-01

    Full Text Available Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly “tuned,” can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P1,P4-diadenosine tetraphosphate (Ap4A, and P1,P5-diadenosine pentaphosphate (Ap5A are present in different ocular locations and therefore they may contribute/modulate inflammatory processes. Adenosine receptors, in particular A2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A3 receptor, selective agonists like N6-(3-iodobenzyl-5′-N-methylcarboxamidoadenosine (CF101 have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large intraocular pressure increases can produce a release of ATP from ocular sensory innervation or after injury to ocular tissues. Then, ATP will activate purinergic P2 receptors present in sensory nerve endings, the iris, the ciliary body, or other tissues surrounding the anterior chamber of the eye to produce uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation.

  6. Inflammation, Fracture and Bone Repair

    Science.gov (United States)

    Loi, Florence; Córdova, Luis A.; Pajarinen, Jukka; Lin, Tzu-hua; Yao, Zhenyu; Goodman, Stuart B.

    2016-01-01

    The reconstitution of lost bone is a subject that is germane to many orthopaedic conditions including fractures and non-unions, infection, inflammatory arthritis, osteoporosis, osteonecrosis, metabolic bone disease, tumors, and periprosthetic particle-associated osteolysis. In this regard, the processes of acute and chronic inflammation play an integral role. Acute inflammation is initiated by endogenous or exogenous adverse stimuli, and can become chronic in nature if not resolved by normal homeostatic mechanisms. Dysregulated inflammation leads to increased bone resorption and suppressed bone formation. Crosstalk amongst inflammatory cells (polymorphonuclear leukocytes and cells of the monocyte-macrophage-osteoclast lineage) and cells related to bone healing (cells of the mesenchymal stem cell-osteoblast lineage and vascular lineage) is essential to the formation, repair and remodeling of bone. In this review, the authors provide a comprehensive summary of the literature related to inflammation and bone repair. Special emphasis is placed on the underlying cellular and molecular mechanisms, and potential interventions that can favorably modulate the outcome of clinical conditions that involve bone repair. PMID:26946132

  7. Targeting inflammation in metabolic syndrome.

    Science.gov (United States)

    Welty, Francine K; Alfaddagh, Abdulhamied; Elajami, Tarec K

    2016-01-01

    The metabolic syndrome (MetS) is comprised of a cluster of closely related risk factors, including visceral adiposity, insulin resistance, hypertension, high triglyceride, and low high-density lipoprotein cholesterol; all of which increase the risk for the development of type 2 diabetes and cardiovascular disease. A chronic state of inflammation appears to be a central mechanism underlying the pathophysiology of insulin resistance and MetS. In this review, we summarize recent research which has provided insight into the mechanisms by which inflammation underlies the pathophysiology of the individual components of MetS including visceral adiposity, hyperglycemia and insulin resistance, dyslipidemia, and hypertension. On the basis of these mechanisms, we summarize therapeutic modalities to target inflammation in the MetS and its individual components. Current therapeutic modalities can modulate the individual components of MetS and have a direct anti-inflammatory effect. Lifestyle modifications including exercise, weight loss, and diets high in fruits, vegetables, fiber, whole grains, and low-fat dairy and low in saturated fat and glucose are recommended as a first line therapy. The Mediterranean and dietary approaches to stop hypertension diets are especially beneficial and have been shown to prevent development of MetS. Moreover, the Mediterranean diet has been associated with reductions in total and cardiovascular mortality. Omega-3 fatty acids and peroxisome proliferator-activated receptor α agonists lower high levels of triglyceride; their role in targeting inflammation is reviewed. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone blockers comprise pharmacologic therapies for hypertension but also target other aspects of MetS including inflammation. Statin drugs target many of the underlying inflammatory pathways involved in MetS. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Prenatal Inflammation Linked to Autism Risk

    Science.gov (United States)

    ... Thursday, January 24, 2013 Prenatal inflammation linked to autism risk Maternal inflammation during early pregnancy may be related to an increased risk of autism in children, according to new findings supported by ...

  9. Aetiological factors behind adipose tissue inflammation

    DEFF Research Database (Denmark)

    von Scholten, Bernt J; Andresen, Erik N; Sørensen, Thorkild I A

    2013-01-01

    Despite extensive research into the biological mechanisms behind obesity-related inflammation, knowledge of environmental and genetic factors triggering such mechanisms is limited. In the present narrative review we present potential determinants of adipose tissue inflammation and suggest ways...

  10. Actemra Approved for Certain Blood Vessel Inflammation

    Science.gov (United States)

    ... 165836.html Actemra Approved for Certain Blood Vessel Inflammation Drug will treat adults with a condition called ... to treat adults with giant cell arteritis, an inflammation of the blood vessels (vasculitis). In a media ...

  11. The coagulant response in sepsis and inflammation

    NARCIS (Netherlands)

    Levi, M. [=Marcel M.

    2010-01-01

    Critically ill patients often have systemic activation of both inflammation and coagulation. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation not only leads to activation of coagulation, but coagulation also considerably affects inflammatory

  12. Anemia of Inflammation and Chronic Disease

    Science.gov (United States)

    ... Anemia of inflammation and chronic disease is a type of anemia that commonly occurs with chronic, or long term, ... inflammation and chronic disease (AI/ACD) is a type of anemia that commonly occurs with chronic illnesses, infections, cancer, ...

  13. Relationship between Inflammation and Cardiovascular Diseases

    OpenAIRE

    Riddhi Patel; Henish Patel; Rachana Sarawade

    2013-01-01

    Inflammation is a part of complex biological response of vascular tissue to harmful stimuli such as pathogens, damaged cells or irritants. Recent advance in basic science have established a fundamental role for inflammation immediating all stages of cardiovascular diseases from initiation, progression and complications. Inflammation is thread linking to cardiovascular diseases. Clinical studies have shown that this emerging biology of inflammation play important role in pathogenesis of acute ...

  14. Gulf War Illness Inflammation Reduction Trial

    Science.gov (United States)

    2015-10-01

    1 AWARD NUMBER: W81XWH-14-1-0477 TITLE: Gulf War Illness Inflammation Reduction Trial PRINCIPAL INVESTIGATOR: Ronald R. Bach, Ph.D...5a. CONTRACT NUMBER Gulf War Illness Inflammation Reduction Trial 5b. GRANT NUMBER W81XWH-14-1-0477 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...GWI). Elevated biomarkers of inflammation were observed in our pilot observational study of GWI. Thus, chronic inflammation appears to be part of

  15. SOCS and inflammation in chronic renal failure

    OpenAIRE

    Rastmanesh, M.M.

    2008-01-01

    Atherosclerosis is the major cause of morbidity and mortality in renal patients and a major health concern in western countries per se. Recent studies point to the important role of inflammation as an underlying cause of atherosclerosis. Importantly medicines that suppress inflammation lower the incidence of atherosclerosis as well. This indicates the importance of molecules that are able to control inflammation. Inflammation in renal patients is characterized by increased plasma levels of in...

  16. Kostens betydning for parodontal inflammation

    DEFF Research Database (Denmark)

    Damgaard, Christian

    2017-01-01

    Nærværende artikel præsenterer en oversigt over den foreliggende viden om kostens betydning for parodontal inflammation. Der er i vekslende grad dokumentation for sammenhænge mellem kost og marginal parodontitis (MP). I forbindelse med behandlingen af MP lader indtaget af antioxidanter og...... flerumættede fedtsyrer til at bidrage gunstigt til helingen af MP. Med baggrund i forøget viden om kostens betydning for udviklingen af parodontal inflammation bør tandlæger også rådgive om kost, for derigennem at styrke behandlingen af patienter med MP og de systemiske sygdomme, som MP forårsager en øget...

  17. Metabolic triggered inflammation in osteoarthritis.

    Science.gov (United States)

    Wang, X; Hunter, D; Xu, J; Ding, C

    2015-01-01

    Osteoarthritis (OA) is a common chronic joint disorder with a multifactorial etiology including genetic and environmental factors. Metabolic triggered inflammation, induced by nutrient overload and metabolic surplus, consists of components such as obesity, pro-inflammatory cytokines and adipokines, abnormal metabolites, acute phase proteins, vitamin D deficiency, and deregulated microRNAs that may play a role in OA pathophysiology. Obesity-related metabolic factors, especially adipokines, contribute to OA development by inducing pro-inflammatory cytokines and degradative enzymes, leading to cartilage matrix impairment and subchondral bone remodeling. Ectopic metabolite deposition and low-grade systemic inflammation can contribute to a toxic internal environment that exacerbates OA. Complement components highly expressed in osteoarthritic joints have also been proposed as causative factors. Vitamin D deficiency has been associated with obesity and is implicated to be associated with cartilage loss in OA. Metabolic microRNAs may explain the inflammatory link between obesity and OA. Therapies targeting metabolic-triggered inflammation and its components are anticipated to have potential for the treatment of OA. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  18. Monocyte Conversion During Inflammation and Injury.

    Science.gov (United States)

    Kratofil, Rachel M; Kubes, Paul; Deniset, Justin F

    2017-01-01

    Monocytes are circulating leukocytes important in both innate and adaptive immunity, primarily functioning in immune defense, inflammation, and tissue remodeling. There are 2 subsets of monocytes in mice (3 subsets in humans) that are mobilized from the bone marrow and recruited to sites of inflammation, where they carry out their respective functions in promoting inflammation or facilitating tissue repair. Our understanding of the fate of these monocyte subsets at the site of inflammation is constantly evolving. This brief review highlights the plasticity of monocyte subsets and their conversion during inflammation and injury. © 2016 American Heart Association, Inc.

  19. Obesity and Inflammation: Epidemiology, Risk Factors, and Markers of Inflammation

    Directory of Open Access Journals (Sweden)

    Heriberto Rodríguez-Hernández

    2013-01-01

    Full Text Available Obesity is a public health problem that has reached epidemic proportions with an increasing worldwide prevalence. The global emergence of obesity increases the risk of developing chronic metabolic disorders. Thus, it is an economic issue that increased the costs of the comorbidities associated. Moreover, in recent years, it has been demonstrated that obesity is associated with chronic systemic inflammation, this status is conditioned by the innate immune system activation in adipose tissue that promotes an increase in the production and release of pro-inflammatory cytokines that contribute to the triggering of the systemic acute-phase response which is characterized by elevation of acute-phase protein levels. On this regard, low-grade chronic inflammation is a characteristic of various chronic diseases such as metabolic syndrome, cardiovascular disease, diabetes, hypertension, non-alcoholic fatty liver disease, and some cancers, among others, which are also characterized by obesity condition. Thus, a growing body of evidence supports the important role that is played by the inflammatory response in obesity condition and the pathogenesis of chronic diseases related.

  20. Osteocalcin expression in pulp inflammation.

    Science.gov (United States)

    Abd-Elmeguid, Ashraf; Abdeldayem, Marwa; Kline, Loren W; Moqbel, Redwan; Vliagoftis, Harrisios; Yu, Donald C

    2013-07-01

    Dental pulp inflammation and repair are closely related. Osteocalcin (OCN), a glycoprotein present in dentin matrix, is expressed by odontoblasts. Although OCN is considered a reparative molecule inside the dental pulp, it is not clear if it is involved in pulpal inflammation. The objective of this study was to localize OCN in reversible and irreversible pulpitis and to describe its possible function in inflammation. Pulp tissues in the form of reversible and irreversible pulpitis were collected from the endodontic clinic. Those from impacted teeth were used as controls. Immunohistochemistry was used to localize OCN. Samples were analyzed for OCN and inflammatory mediator expression using multiplex assay. OCN in inflamed tissues was localized in cells and matrix around calcification areas and in cells around blood vessels but not in normal tissues. The plex assay (Bio-Plex 200, Bio-Rad Laboratories Ltd, Mississauga, ON, Canada) showed OCN expression in reversible pulpitis significantly higher than in irreversible pulpitis, and both were significantly higher than in the controls. A panel of inflammatory mediators showed an increase in reversible and irreversible pulpitis. Another panel was decreased in both stages compared with the controls. OCN expression in reversible pulpitis was positively correlated to the expression of vascular endothelial growth factor, fibroblast growth factor, macrophage inflammatory protein-1β, monocyte-derived chemokine, monocyte chemoattractant protein-1, interleukin (IL)-17, and soluble IL-2 receptor α and negatively correlated to that of IL-1α, IL-1β, IL-8, granulocyte macrophage colony-stimulating factor, and macrophage inflammatory protein-1α. Profound understanding of the pulp inflammatory process would lead to new molecular treatment strategies. Our data indicate that OCN expression in reversible pulpitis is associated with angiogenic markers, suggesting its potential use in regenerative treatment. Copyright © 2013 American

  1. Chemokines in cancer related inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Allavena, Paola; Germano, Giovanni; Marchesi, Federica [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089, Rozzano, Milan (Italy); Mantovani, Alberto, E-mail: alberto.mantovani@humanitasresearch.it [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089, Rozzano, Milan (Italy); Department of Translational Medicine, University of Milan (Italy)

    2011-03-10

    Chemokines are key players of the cancer-related inflammation. Chemokine ligands and receptors are downstream of genetic events that cause neoplastic transformation and are abundantly expressed in chronic inflammatory conditions which predispose to cancer. Components of the chemokine system affect multiple pathways of tumor progression including: leukocyte recruitment, neo-angiogenesis, tumor cell proliferation and survival, invasion and metastasis. Evidence in pre-clinical and clinical settings suggests that the chemokine system represents a valuable target for the development of innovative therapeutic strategies.

  2. Inflammation and cancer stem cells.

    Science.gov (United States)

    Shigdar, Sarah; Li, Yong; Bhattacharya, Santanu; O'Connor, Michael; Pu, Chunwen; Lin, Jia; Wang, Tao; Xiang, Dongxi; Kong, Lingxue; Wei, Ming Q; Zhu, Yimin; Zhou, Shufeng; Duan, Wei

    2014-04-10

    Cancer stem cells are becoming recognised as being responsible for metastasis and treatment resistance. The complex cellular and molecular network that regulates cancer stem cells and the role that inflammation plays in cancer progression are slowly being elucidated. Cytokines, secreted by tumour associated immune cells, activate the necessary pathways required by cancer stem cells to facilitate cancer stem cells progressing through the epithelial-mesenchymal transition and migrating to distant sites. Once in situ, these cancer stem cells can secrete their own attractants, thus providing an environment whereby these cells can continue to propagate the tumour in a secondary niche. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Obstructive sleep apnea and inflammation.

    LENUS (Irish Health Repository)

    McNicholas, Walter T

    2012-02-01

    The pathogenesis of cardiovascular complications in obstructive sleep apnea syndrome (OSAS) is not fully understood but is likely multifactorial in origin. Inflammatory processes play an important role in the pathogenesis of atherosclerosis, and circulating levels of several markers of inflammation have been associated with future cardiovascular risk. These include cell adhesion molecules such as intercellular adhesion molecule-1 and selectins, cytokines such as tumour necrosis factor alpha and interleukin 6, chemokines such as interleukin 8, and C-reactive protein. There is also increasing evidence that inflammatory processes play an important role in the cardiovascular pathophysiology of OSAS and many of the inflammatory markers associated with cardiovascular risk have been reported as elevated in patients with OSAS. Furthermore, animal and cell culture studies have demonstrated preferential activation of inflammatory pathways by intermittent hypoxia, which is an integral feature of OSAS. The precise role of inflammation in the development of cardiovascular disease in OSAS requires further study, particularly the relationship with oxidative stress, metabolic dysfunction, and obesity.

  4. Growth hormone, inflammation and aging

    Directory of Open Access Journals (Sweden)

    Michal M. Masternak

    2012-04-01

    Full Text Available Mutant animals characterized by extended longevity provide valuable tools to study the mechanisms of aging. Growth hormone and insulin-like growth factor-1 (IGF-1 constitute one of the well-established pathways involved in the regulation of aging and lifespan. Ames and Snell dwarf mice characterized by GH deficiency as well as growth hormone receptor/growth hormone binding protein knockout (GHRKO mice characterized by GH resistance live significantly longer than genetically normal animals. During normal aging of rodents and humans there is increased insulin resistance, disruption of metabolic activities and decline of the function of the immune system. All of these age related processes promote inflammatory activity, causing long term tissue damage and systemic chronic inflammation. However, studies of long living mutants and calorie restricted animals show decreased pro-inflammatory activity with increased levels of anti-inflammatory adipokines such as adiponectin. At the same time, these animals have improved insulin signaling and carbohydrate homeostasis that relate to alterations in the secretory profile of adipose tissue including increased production and release of anti-inflammatory adipokines. This suggests that reduced inflammation promoting healthy metabolism may represent one of the major mechanisms of extended longevity in long-lived mutant mice and likely also in the human.

  5. Purinergic signaling during intestinal inflammation.

    Science.gov (United States)

    Longhi, Maria Serena; Moss, Alan; Jiang, Zhenghui Gordon; Robson, Simon C

    2017-09-01

    Inflammatory bowel disease (IBD) is a devastating disease that is associated with excessive inflammation in the intestinal tract in genetically susceptible individuals and potentially triggered by microbial dysbiosis. This illness markedly predisposes patients to thrombophilia and chronic debility as well as bowel, lymphatic, and liver cancers. Development of new therapies is needed to re-establish long-term immune tolerance in IBD patients without increasing the risk of opportunistic infections and cancer. Aberrant purinergic signaling pathways have been implicated in disordered thromboregulation and immune dysregulation, as noted in the pathogenesis of IBD and other gastrointestinal/hepatic autoimmune diseases. Expression of CD39 on endothelial or immune cells allows for homeostatic integration of hemostasis and immunity, which are disrupted in IBD. Our focus in this review is on novel aspects of the functions of CD39 and related NTPDases in IBD. Regulated CD39 activity allows for scavenging of extracellular nucleotides, the maintenance of P2-receptor integrity and coordination of adenosinergic signaling responses. CD39 together with CD73, serves as an integral component of the immunosuppressive machinery of dendritic cells, myeloid cells, T and B cells. Genetic inheritance and environental factors closely regulate the levels of expression and phosphohydrolytic activity of CD39, both on immune cells and released microparticles. Purinergic mechanisms associated with T regulatory and supressor T helper type 17 cells modulate disease activity in IBD, as can be modeled in experimental colitis. As a recent example, upregulation of CD39 is dependent upon ligation of the aryl hydrocarbon receptor (AHR), as with natural ligands such as bilirubin and 2-(1' H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). Decreased expression of CD39 and/or dysfunctional AHR signaling, however, abrogates the protective effects of immunosuppressive AHR ligands. These

  6. Insulin resistance and chronic inflammation

    Directory of Open Access Journals (Sweden)

    Natalia Matulewicz

    2016-12-01

    Full Text Available Insulin resistance is a condition of reduced biological response to insulin. Growing evidence indicates the role of the chronic low-grade inflammatory response in the pathogenesis of insulin resistance. Adipose tissue in obesity is characterized by increased lipolysis with the excessive release of free fatty acids, and is also a source of proinflammatory cytokines. Both these factors may inhibit insulin action. Proinflammatory cytokines exert their effect by stimulating major inflammatory NFκB and JNK pathways within the cells. Inflammatory processes in other insulin responsive tissues may also play a role in inducing insulin resistance. This paper is an overview of the chronic low-grade inflammation in adipose tissue, skeletal muscle, liver and endothelial cells during the development of insulin resistance.

  7. Microbiota, Inflammation and Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Cécily Lucas

    2017-06-01

    Full Text Available Colorectal cancer, the fourth leading cause of cancer-related death worldwide, is a multifactorial disease involving genetic, environmental and lifestyle risk factors. In addition, increased evidence has established a role for the intestinal microbiota in the development of colorectal cancer. Indeed, changes in the intestinal microbiota composition in colorectal cancer patients compared to control subjects have been reported. Several bacterial species have been shown to exhibit the pro-inflammatory and pro-carcinogenic properties, which could consequently have an impact on colorectal carcinogenesis. This review will summarize the current knowledge about the potential links between the intestinal microbiota and colorectal cancer, with a focus on the pro-carcinogenic properties of bacterial microbiota such as induction of inflammation, the biosynthesis of genotoxins that interfere with cell cycle regulation and the production of toxic metabolites. Finally, we will describe the potential therapeutic strategies based on intestinal microbiota manipulation for colorectal cancer treatment.

  8. Dual role of neutrophils in inflammation

    NARCIS (Netherlands)

    Pillay, J.

    2011-01-01

    Systemic inflammation is a hallmark of trauma, sepsis and various severe infectious diseases. Severe systemic inflammation can lead to inflammatory complications. The Acute Respiratory Distress Syndrome (ARDS) and Multiple Organ Dysfunction Syndrome (MODS) are seen after trauma and in sepsis and are

  9. Influence of Inflammation on Voriconazole Metabolism

    NARCIS (Netherlands)

    Ventura, M. A. Encalada; Span, L. F. R.; van den Heuvel, E. R.; Groothuis, G. M. M.; Alffenaar, J. -W. C.

    Voriconazole pharmacokinetics shows a large inter- and intrapatient variability. Inflammation is associated with changes in the expression of CYP isoenzymes. Here, we evaluated the influence of inflammation, marked by C-reactive protein (CRP) levels in blood, on the metabolism of voriconazole.

  10. Reparative inflammation takes charge of tissue regeneration

    NARCIS (Netherlands)

    Karin, Michael; Clevers, Hans

    2016-01-01

    Inflammation underlies many chronic and degenerative diseases, but it also mitigates infections, clears damaged cells and initiates tissue repair. Many of the mechanisms that link inflammation to damage repair and regeneration in mammals are conserved in lower organisms, indicating that it is an

  11. Radiopharmaceuticals for imaging chronic lymphocytic inflammation

    NARCIS (Netherlands)

    Malviya, Gaurav; De Vries, Erik F. J.; Dierckx, Rudi A.; Signore, Alberto

    In the last few decades, a number of radiopharmaceuticals for imaging inflammation have been proposed that differ in their specificity and mechanism of uptake in inflamed foci as compared to the traditional inflammation imaging agents. Radiolabelled cytokines represent a reliable tool for the

  12. Inflammation: Friend or foe for animal production?

    Science.gov (United States)

    Inflammation is an essential immune response that seeks to contain microbial infection and repair damaged tissue. Increased pro-inflammatory mediators have been associated with enhanced resistance to a range of important poultry and pig pathogens. However, inflammation may also have undesirable co...

  13. Neurogenic inflammation in human and rodent skin

    DEFF Research Database (Denmark)

    Schmelz, M; Petersen, Lars Jelstrup

    2001-01-01

    The combination of vasodilation and protein extravasation following activation of nociceptors has been termed "neurogenic inflammation." In contrast to rodents, no neurogenic protein extravasation can be elicited in healthy human skin. Dermal microdialysis has considerably increased our knowledge...... about neurogenic inflammation in human skin, including the involvement of mast cells....

  14. The impact of inflammation on respiratory plasticity.

    Science.gov (United States)

    Hocker, Austin D; Stokes, Jennifer A; Powell, Frank L; Huxtable, Adrianne G

    2017-01-01

    Breathing is a vital homeostatic behavior and must be precisely regulated throughout life. Clinical conditions commonly associated with inflammation, undermine respiratory function may involve plasticity in respiratory control circuits to compensate and maintain adequate ventilation. Alternatively, other clinical conditions may evoke maladaptive plasticity. Yet, we have only recently begun to understand the effects of inflammation on respiratory plasticity. Here, we review some of common models used to investigate the effects of inflammation and discuss the impact of inflammation on nociception, chemosensory plasticity, medullary respiratory centers, motor plasticity in motor neurons and respiratory frequency, and adaptation to high altitude. We provide new data suggesting glial cells contribute to CNS inflammatory gene expression after 24h of sustained hypoxia and inflammation induced by 8h of intermittent hypoxia inhibits long-term facilitation of respiratory frequency. We also discuss how inflammation can have opposite effects on the capacity for plasticity, whereby it is necessary for increases in the hypoxic ventilatory response with sustained hypoxia, but inhibits phrenic long term facilitation after intermittent hypoxia. This review highlights gaps in our knowledge about the effects of inflammation on respiratory control (development, age, and sex differences). In summary, data to date suggest plasticity can be either adaptive or maladaptive and understanding how inflammation alters the respiratory system is crucial for development of better therapeutic interventions to promote breathing and for utilization of plasticity as a clinical treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Susceptibility to chronic inflammation: an update.

    Science.gov (United States)

    Nasef, Noha Ahmed; Mehta, Sunali; Ferguson, Lynnette R

    2017-03-01

    Chronic inflammation is defined by the persistence of inflammatory processes beyond their physiological function, resulting in tissue destruction. Chronic inflammation is implicated in the progression of many chronic diseases and plays a central role in chronic inflammatory and autoimmune disease. As such, this review aims to collate some of the latest research in relation to genetic and environmental susceptibilities to chronic inflammation. In the genetic section, we discuss some of the updates in cytokine research and current treatments that are being developed. We also discuss newly identified canonical and non-canonical genes associated with chronic inflammation. In the environmental section, we highlight some of the latest updates and evidence in relation to the role that infection, diet and stress play in promoting inflammation. The aim of this review is to provide an overview of the latest research to build on our current understanding of chronic inflammation. It highlights the complexity associated with chronic inflammation, as well as provides insights into potential new targets for therapies that could be used to treat chronic inflammation and consequently prevent disease progression.

  16. Lipid profile, hyperglycaemia, systemic inflammation and ...

    African Journals Online (AJOL)

    Lipid profile, hyperglycaemia, systemic inflammation and anthropometry as cardiovascular risk factors and their association with dietary intakes in children from rural Cofimvaba, Eastern Cape, South Africa. ... Hyperglycaemia and systemic inflammation was also prevalent, but no obesity was observed. Healthy lifestyles ...

  17. SOCS and inflammation in chronic renal failure

    NARCIS (Netherlands)

    Rastmanesh, M.M.

    2008-01-01

    Atherosclerosis is the major cause of morbidity and mortality in renal patients and a major health concern in western countries per se. Recent studies point to the important role of inflammation as an underlying cause of atherosclerosis. Importantly medicines that suppress inflammation lower the

  18. Inflammation, a Key Factor in Cancer Ambush

    Directory of Open Access Journals (Sweden)

    Omolbanin Amjadi

    2014-05-01

    Full Text Available Inflammatory condition is the consequence of defensive mechanism of immune system against viral and bacterial infection, tissue injury, UV radiation, stress and etc. Persistently acute inflammation leads to chronic phase which is characterized by production of pro-inflammatory mediators from T cells. These molecules (e.g. IL-6, TNF-&alpha, IL-1&beta and IL-17 are mostly pleiotropic cytokines involved in multiple signaling cascades. NF-&kappaB, STAT3, and HIF-1&alpha are the major engaged pathways directing to several downstream targets associating with tumorigenesis and inflammation. Carcinogenesis processes such as DNA mutation/damage, proliferation, angiogenesis, apoptosis, and invasion are implicated to inflammation. Clearly there is a closely association between cancer and inflammation reported as “Seven Hallmark of Cancer”. The elucidation of relationship between inflammation and cancer and their interaction may result in effective therapy and prevention. Gastric cancer is one of the main cancer involved in complex correlation of inflammation and cancer. Inflammation in gastric epithelium could trigger cellular transformation and promote invasion by inducing immune responses and utilizing signaling cascades. Gastric tumor microenvironment has inverse association by providing cytokines and inflammatory mediators. This closely relationship facilitates gastric tumor development and the induction of chronic inflammation in tumor microenvironment. The current review will focus on describing the possible and critical ways in which inflammation and cancer are linked together with specific view to gastric cancer and inflammation. Finally, it introduces some putative treatment generally used in this way in order to direct more attention for further exploration.

  19. Assessment of in situ adipose tissue inflammation by microdialysis

    DEFF Research Database (Denmark)

    Langkilde, Anne; Andersen, Ove; Henriksen, Jens H

    2015-01-01

    Inflammation, and specifically adipose tissue (AT) inflammation, is part of the pathophysiology of obesity and HIV-associated lipodystrophy. Local AT protein assessment methods are limited, and AT inflammation studies have therefore primarily examined inflammatory gene expression. We therefore...

  20. Preeclampsia: From Inflammation to Immunoregulation

    Directory of Open Access Journals (Sweden)

    Denise C Cornelius

    2018-01-01

    Full Text Available Preeclampsia (PE affects 5% to 7% of pregnant women each year worldwide, accounts for up to 18% of maternal deaths in the United States each year, and is the number 1 cause of premature births. Preeclampsia is associated with hypertension after the 20th week of gestation with or without proteinuria, in conjunction with fetal growth restriction, maternal endothelial dysfunction, and chronic immune activation. The mechanisms leading to the development of PE are unclear. However, it is thought that shallow trophoblast invasion and insufficient remodeling of uterine spiral arteries result in placental ischemia. Consequently, an immune imbalance characterized by increases in proinflammatory CD4 + T cells and cytokines along with decreases in regulatory T cells and anti-inflammatory cytokines occurs. This imbalance leads to chronic inflammation and ensuing oxidative stress, proinflammatory cytokines, and autoantibodies. Studies performed in our laboratories, using the R educed U terine P erfusion P ressure (RUPP rat model of placental ischemia, have demonstrated a role for this immune imbalance to mediate PE pathophysiology and identified potential mechanisms of immunoregulation that may be of benefit in the treatment of PE. Therefore, the purpose of this commentary is to review studies demonstrating the positive effects of immunoregulatory factors in the RUPP rat model of PE. Restoration of the immune balance in PE may be a potential strategy for the development of therapeutic interventions that could improve maternal and fetal outcomes associated with this maternal syndrome.

  1. Red cell DAMPs and inflammation.

    Science.gov (United States)

    Mendonça, Rafaela; Silveira, Angélica A A; Conran, Nicola

    2016-09-01

    Intravascular hemolysis, or the destruction of red blood cells in the circulation, can occur in numerous diseases, including the acquired hemolytic anemias, sickle cell disease and β-thalassemia, as well as during some transfusion reactions, preeclampsia and infections, such as those caused by malaria or Clostridium perfringens. Hemolysis results in the release of large quantities of red cell damage-associated molecular patterns (DAMPs) into the circulation, which, if not neutralized by innate protective mechanisms, have the potential to activate multiple inflammatory pathways. One of the major red cell DAMPs, heme, is able to activate converging inflammatory pathways, such as toll-like receptor signaling, neutrophil extracellular trap formation and inflammasome formation, suggesting that this DAMP both activates and amplifies inflammation. Other potent DAMPs that may be released by the erythrocytes upon their rupture include heat shock proteins (Hsp), such as Hsp70, interleukin-33 and Adenosine 5' triphosphate. As such, hemolysis represents a major inflammatory mechanism that potentially contributes to the clinical manifestations that have been associated with the hemolytic diseases, such as pulmonary hypertension and leg ulcers, and likely plays a role in specific complications of sickle cell disease such as endothelial activation, vaso-occlusive processes and tissue injury.

  2. Nonspecific inflammation in the face

    Energy Technology Data Exchange (ETDEWEB)

    Hyun, Young Min; Park, Rae Chung; Jung, Hwan Sug; Choi, Soon Chul; Park, Tae Won; You, Dong Soo [Dept. of Oral and Maxillofacial Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1997-02-15

    Patient with complaints of swelling, pain in the maxillary region and discomfort visited Seoul National University Dental Hospital in August last year. Clinical examination and diagnostic imagings implied he was suffered from fungal hyphal infection but no causative fungus was found by the histopathologic and microbiologic investigation. Therefore he was diagnosed with nonspecific inflammation. But as yet, we do think this case is very similar to some kinds of mucomycosis. So we presented this case for more thorough discussion. Following are founded in the examination. 1. Patient had suffered from Diabetes mellitus and complained of stuffiness, headache, swelling in buccal cheeks and paraesthesia. And we found more maxillary bony destruction and ulcer with elevated margin in the palate by clinical examination. 2. In the first visit, Plain films revealed general bony destruction of the maxilla, radiopaqueness in the sinonasal cavities. CT and MRI showed soft tissue mass filled in the paranasal sinus except frontal sinus and bony destruction in in valved bones. 3. No causative bacteria and fungus was found in the biopsy and microbiologic cultures. 4. Caldwell-Luc operation and curettage were carried and antibiotics were taken for 4 months. But now he was worse than in the past. 5. In the second visit, involvement of orbit, parapharyngeal sinus, clivus, cavernous sinus and middle cranial fossa we re seen clearly in the CT and MRI.

  3. Inflammation and coagulation in atherosclerosis.

    Science.gov (United States)

    Krychtiuk, K A; Kastl, S P; Speidl, W S; Wojta, J

    2013-01-01

    Cardiovascular diseases remain to be the leading cause of death in Western societies. Despite major findings in vascular biology that lead to a better understanding of the pathomechanisms involved in atherosclerosis, treatment of the disease has only changed slightly within the last years. A big body of evidence suggests that atherosclerosis is a chronic inflammatory disease of the vessel wall. Accumulation and peroxidation of LDL-particles within the vessel wall trigger a strong inflammatory response, causing macrophage and T-cell accumulation within the vessel wall. Additionally, B-cells and specific antibodies against LDL-particles, as well as the complement system are implicated in atherogenesis. Besides data from clinical trials and autopsy studies it was the implementation of mouse models of atherosclerosis and the emerging field of direct gen-modification that lead to a thorough description of the pathophysiological mechanisms involved in the disease and created overwhelming evidence for a participation of the immune system. Recently, the cross-talk between coagulation and inflammation in atherogenesis has gained attention. Serious limitations and disparities in the pathophysiology of atherosclerosis in mice and men complicated the translation of experimental data into clinical practice. Despite these limitations, new anti-inflammatory medical therapies in cardiovascular disease are currently being tested in clinical trials.

  4. Rhinoviruses, Allergic Inflammation, and Asthma

    Science.gov (United States)

    Gavala, Monica; Bertics, Paul J.; Gern, James E.

    2011-01-01

    Summary Viral infections affect wheezing and asthma in children and adults of all ages. In infancy, wheezing illnesses are usually viral in origin, and children with more severe wheezing episodes are more likely to develop recurrent episodes of asthma and to develop asthma later in childhood. Children who develop allergen-specific immunoglobulin E (allergic sensitization), and those who wheeze with rhinoviruses (HRV) are at especially high risk for asthma. In older children and adults, HRV infections generally cause relatively mild respiratory illnesses and yet contribute to acute and potentially severe exacerbations in patients with asthma. These findings underline the importance of understanding the synergistic nature of allergic sensitization and infections with HRV in infants relative to the onset of asthma and in children and adults with respect to exacerbations of asthma. This review discusses clinical and experimental evidence of virus/allergen interactions and evaluates theories which relate immunologic responses to respiratory viruses and allergens to the pathogenesis and disease activity of asthma. Greater understanding of the relationship between viral respiratory infections, allergic inflammation, and asthma is likely to suggest new strategies for the prevention and treatment of asthma. PMID:21682739

  5. Resolution of inflammation in Alzheimer’s disease

    OpenAIRE

    Wang, Xiuzhe

    2014-01-01

    Inflammation is associated with Alzheimer’s disease (AD), a neurodegenerative disorder with no cure up to date. Ample evidence from studies within various disciplines support that inflammation plays a role in AD. Resolution of inflammation is the end stage of inflammation, where the detrimental effects of inflammation are terminated and tissue healing is initiated. Cutting-edge research has demonstrated that resolution of inflammation is c...

  6. A link between inflammation and metastasis

    DEFF Research Database (Denmark)

    Hansen, M. T.; Forst, B.; Cremers, N.

    2015-01-01

    S100A4 is implicated in metastasis and chronic inflammation, but its function remains uncertain. Here we establish an S100A4-dependent link between inflammation and metastatic tumor progression. We found that the acute-phase response proteins serum amyloid A (SAA) 1 and SAA3 are transcriptional....... Furthermore, coordinate expression of S100A4 and SAA in tumor samples from colorectal carcinoma patients significantly correlated with reduced overall survival. These data show that SAA proteins are effectors for the metastasis-promoting functions of S100A4, and serve as a link between inflammation and tumor...

  7. Virus induced inflammation and cancer development.

    Science.gov (United States)

    Read, Scott A; Douglas, Mark W

    2014-04-10

    Chronic inflammation as a result of viral infection significantly increases the likelihood of cancer development. A handful of diverse viruses have confirmed roles in cancer development and progression, but the list of suspected oncogenic viruses is continually growing. Viruses induce cancer directly and indirectly, by activating inflammatory signalling pathways and cytokines, stimulating growth of infected cells and inhibiting apoptosis. Although oncogenic viruses induce inflammation by various mechanisms, it is generally mediated by the MAPK, NFκB and STAT3 signalling pathways. This review will explore the unique mechanisms by which different oncogenic viruses induce inflammation to promote cancer initiation and progression. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Cannabinoids in intestinal inflammation and cancer.

    Science.gov (United States)

    Izzo, Angelo A; Camilleri, Michael

    2009-08-01

    Emerging evidence suggests that cannabinoids may exert beneficial effects in intestinal inflammation and cancer. Adaptive changes of the endocannabinoid system have been observed in intestinal biopsies from patients with inflammatory bowel disease and colon cancer. Studies on epithelial cells have shown that cannabinoids exert antiproliferative, antimetastatic and apoptotic effects as well as reducing cytokine release and promoting wound healing. In vivo, cannabinoids - via direct or indirect activation of CB(1) and/or CB(2) receptors - exert protective effects in well-established models of intestinal inflammation and colon cancer. Pharmacological elevation of endocannabinoid levels may be a promising strategy to counteract intestinal inflammation and colon cancer.

  9. Neuro-Sweet Disease Causing Orbital Inflammation.

    Science.gov (United States)

    Taravati, Parisa

    2015-02-01

    Neuro-Sweet disease is a rare condition causing encephalitis or meningitis in addition to the erythematous skin plaques of Sweet syndrome. Neuro-Sweet disease has been associated with several ocular manifestations, including ocular movement disorders, episcleritis, conjunctivitis, uveitis, and optic disc oedema. The author reports a patient with orbital inflammation, cranial neuropathies, and a skin rash in the setting of myelodysplastic syndrome. Biopsy of her skin lesion confirmed the diagnosis of neuro-Sweet disease. To the author's knowledge, this is the first reported case of neuro-Sweet disease causing orbital inflammation. Her ocular inflammation resolved with the use of systemic corticosteroid treatment.

  10. Cholinergic Regulation of Airway Inflammation and Remodelling

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian

    2012-01-01

    Full Text Available Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD.

  11. The dynamics of acute inflammation

    Science.gov (United States)

    Kumar, Rukmini

    The acute inflammatory response is the non-specific and immediate reaction of the body to pathogenic organisms, tissue trauma and unregulated cell growth. An imbalance in this response could lead to a condition commonly known as "shock" or "sepsis". This thesis is an attempt to elucidate the dynamics of acute inflammatory response to infection and contribute to its systemic understanding through mathematical modeling and analysis. The models of immunity discussed use Ordinary Differential Equations (ODEs) to model the variation of concentration in time of the various interacting species. Chapter 2 discusses three such models of increasing complexity. Sections 2.1 and 2.2 discuss smaller models that capture the core features of inflammation and offer general predictions concerning the design of the system. Phase-space and bifurcation analyses have been used to examine the behavior at various parameter regimes. Section 2.3 discusses a global physiological model that includes several equations modeling the concentration (or numbers) of cells, cytokines and other mediators. The conclusions drawn from the reduced and detailed models about the qualitative effects of the parameters are very similar and these similarities have also been discussed. In Chapter 3, the specific applications of the biologically detailed model are discussed in greater detail. These include a simulation of anthrax infection and an in silico simulation of a clinical trial. Such simulations are very useful to biologists and could prove to be invaluable tools in drug design. Finally, Chapter 4 discusses the general problem of extinction of populations modeled as continuous variables in ODES is discussed. The average time to extinction and threshold are estimated based on analyzing the equivalent stochastic processes.

  12. Prostate cancer and inflammation: the evidence

    Science.gov (United States)

    Sfanos, Karen S; De Marzo, Angelo M

    2014-01-01

    Chronic inflammation is now known to contribute to several forms of human cancer, with an estimated 20% of adult cancers attributable to chronic inflammatory conditions caused by infectious agents, chronic noninfectious inflammatory diseases and / or other environmental factors. Indeed, chronic inflammation is now regarded as an ‘enabling characteristic’ of human cancer. The aim of this review is to summarize the current literature on the evidence for a role for chronic inflammation in prostate cancer aetiology, with a specific focus on recent advances regarding the following: (i) potential stimuli for prostatic inflammation; (ii) prostate cancer immunobiology; (iii) inflammatory pathways and cytokines in prostate cancer risk and development; (iv) proliferative inflammatory atrophy (PIA) as a risk factor lesion to prostate cancer development; and (v) the role of nutritional or other antiinflammatory compounds in reducing prostate cancer risk. PMID:22212087

  13. Inflammation Is Associated with Voriconazole Trough Concentrations

    NARCIS (Netherlands)

    van Wanrooy, Marjolijn J. P.; Span, Lambert F. R.; Rodgers, Michael G. G.; van den Heuvel, Edwin R.; Uges, Donald R. A.; van der Werf, Tjip S.; Kosterink, Jos G. W.; Alffenaar, Jan-Willem C.

    2014-01-01

    Voriconazole concentrations display a large variability, which cannot completely be explained by known factors. Inflammation may be a contributing factor, as inflammatory stimuli can change the activities and expression levels of cytochrome P450 isoenzymes. We explored the correlation between

  14. Red Blood Cell Clearance in Inflammation

    NARCIS (Netherlands)

    Straat, Marleen; van Bruggen, Robin; de Korte, Dirk; Juffermans, Nicole P.

    2012-01-01

    Anemia is a frequently encountered problem in the critically ill patient. The inability to compensate for anemia includes several mechanisms, collectively referred to as anemia of inflammation: reduced production of erythropoietin, impaired bone marrow response to erythropoietin, reduced iron

  15. Neurotrauma and Inflammation: CNS and PNS Responses

    Directory of Open Access Journals (Sweden)

    Bruno Siqueira Mietto

    2015-01-01

    Full Text Available Traumatic injury to the central nervous system (CNS or the peripheral nervous system (PNS triggers a cascade of events which culminate in a robust inflammatory reaction. The role played by inflammation in the course of degeneration and regeneration is not completely elucidated. While, in peripheral nerves, the inflammatory response is assumed to be essential for normal progression of Wallerian degeneration and regeneration, CNS trauma inflammation is often associated with poor recovery. In this review, we discuss key mechanisms that trigger the inflammatory reaction after nervous system trauma, emphasizing how inflammations in both CNS and PNS differ from each other, in terms of magnitude, cell types involved, and effector molecules. Knowledge of the precise mechanisms that elicit and maintain inflammation after CNS and PNS tissue trauma and their effect on axon degeneration and regeneration is crucial for the identification of possible pharmacological drugs that can positively affect the tissue regenerative capacity.

  16. Regulation of pulmonary inflammation by mesenchymal cells

    NARCIS (Netherlands)

    Alkhouri, Hatem; Poppinga, Wilfred Jelco; Tania, Navessa Padma; Ammit, Alaina; Schuliga, Michael

    2014-01-01

    Pulmonary inflammation and tissue remodelling are common elements of chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH). In disease, pulmonary mesenchymal cells not only contribute to tissue

  17. Cannabinoids, Endocannabinoids, and Related Analogs in Inflammation

    National Research Council Canada - National Science Library

    Burstein, Sumner H; Zurier, Robert B

    2009-01-01

    ..., and finally, noncannabinoid components of Cannabis that show anti-inflammatory action. It is intended to be an update on the topic of the involvement of cannabinoids in the process of inflammation...

  18. STRETCHING IMPACTS INFLAMMATION RESOLUTION IN CONNECTIVE TISSUE

    Science.gov (United States)

    Berrueta, Lisbeth; Muskaj, Igla; Olenich, Sara; Butler, Taylor; Badger, Gary J.; Colas, Romain A.; Spite, Matthew; Serhan, Charles N.; Langevin, Helene M.

    2016-01-01

    Acute inflammation is accompanied from its outset by the release of specialized pro-resolving mediators (SPMs), including resolvins, that orchestrate the resolution of local inflammation. We showed earlier that, in rats with subcutaneous inflammation of the back induced by carrageenan, stretching for 10 minutes twice daily reduced inflammation and improved pain, two weeks after carrageenan injection. In this study, we hypothesized that stretching of connective tissue activates local pro-resolving mechanisms within the tissue in the acute phase of inflammation. In rats injected with carrageenan and randomized to stretch vs. no stretch for 48 hours, stretching reduced inflammatory lesion thickness and neutrophil count, and increased resolvin (RvD1) concentrations within lesions. Furthermore, subcutaneous resolvin injection mimicked the effect of stretching. In ex vivo experiments, stretching of connective tissue reduced the migration of neutrophils and increased tissue RvD1 concentration. These results demonstrate a direct mechanical impact of stretching on inflammation-regulation mechanisms within connective tissue. PMID:26588184

  19. Hypothalamic inflammation and gliosis in obesity.

    Science.gov (United States)

    Dorfman, Mauricio D; Thaler, Joshua P

    2015-10-01

    Hypothalamic inflammation and gliosis are recently discovered mechanisms that may contribute to obesity pathogenesis. Current research in this area suggests that investigation of these central nervous system responses may provide opportunities to develop new weight loss treatments. In rodents, hypothalamic inflammation and gliosis occur rapidly with high-fat diet consumption prior to significant weight gain. In addition, sensitivity or resistance to diet-induced obesity in rodents generally correlates with the presence or absence of hypothalamic inflammation and reactive gliosis (brain response to injury). Moreover, functional interventions that increase or decrease inflammation in neurons and glia correspondingly alter diet-associated weight gain. However, some conflicting data have recently emerged that question the contribution of hypothalamic inflammation to obesity pathogenesis. Nevertheless, several studies have detected gliosis and disrupted connectivity in obese humans, highlighting the potential translational importance of this mechanism. There is growing evidence that obesity is associated with brain inflammation in humans, particularly in the hypothalamus where its presence may disrupt body weight control and glucose homeostasis. More work is needed to determine whether this response is common in human obesity and to what extent it can be manipulated for therapeutic benefit.

  20. Inflammation in Complicated Pregnancy and Its Outcome.

    Science.gov (United States)

    Kalagiri, Ram R; Carder, Timothy; Choudhury, Saiara; Vora, Niraj; Ballard, Amie R; Govande, Vinayak; Drever, Nathan; Beeram, Madhava R; Uddin, M Nasir

    2016-12-01

    Background Normal pregnancy relies on a careful balance between immune tolerance and suppression. It is known that strict regulation of maternal immune function, in addition to components of inflammation, is paramount to successful pregnancy, and any imbalance between proinflammatory and anti-inflammatory cytokines and chemokines can lead to aberrant inflammation, often seen in complicated pregnancies. Inflammation in complicated pregnancies is directly associated with increased mortality and morbidity of the mother and offspring. Aberrant inflammatory reactions in complicated pregnancies often lead to adverse outcomes, such as spontaneous abortion, preterm labor, intrauterine growth restriction, and fetal demise. The role of inflammation in different stages of normal pregnancy is reviewed, compared, and contrasted with aberrant inflammation in complicated pregnancies. The complications addressed are preterm labor, pregnancy loss, infection, preeclampsia, maternal obesity, gestational diabetes mellitus, autoimmune diseases, and inflammatory bowel disease. Aim This article examines the role of various inflammatory factors contributing to aberrant inflammation in complicated pregnancies. By understanding the aberrant inflammatory process in complicated pregnancies, novel diagnostic tools and therapeutic interventions for modulating it appropriately can be identified. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  1. Emerging roles of basophils in allergic inflammation

    Directory of Open Access Journals (Sweden)

    Kensuke Miyake

    2017-07-01

    Full Text Available Basophils have long been neglected in immunological studies because they were regarded as only minor relatives of mast cells. However, recent advances in analytical tools for basophils have clarified the non-redundant roles of basophils in allergic inflammation. Basophils play crucial roles in both IgE-dependent and -independent allergic inflammation, through their migration to the site of inflammation and secretion of various mediators, including cytokines, chemokines, and proteases. Basophils are known to produce large amounts of IL-4 in response to various stimuli. Basophil-derived IL-4 has recently been shown to play versatile roles in allergic inflammation by acting on various cell types, including macrophages, innate lymphoid cells, fibroblasts, and endothelial cells. Basophil-derived serine proteases are also crucial for the aggravation of allergic inflammation. Moreover, recent reports suggest the roles of basophils in modulating adaptive immune responses, particularly in the induction of Th2 differentiation and enhancement of humoral memory responses. In this review, we will discuss recent advances in understanding the roles of basophils in allergic inflammation.

  2. Source of Chronic Inflammation in Aging

    Directory of Open Access Journals (Sweden)

    Fumihiro Sanada

    2018-02-01

    Full Text Available Aging is a complex process that results from a combination of environmental, genetic, and epigenetic factors. A chronic pro-inflammatory status is a pervasive feature of aging. This chronic low-grade inflammation occurring in the absence of overt infection has been defined as “inflammaging” and represents a significant risk factor for morbidity and mortality in the elderly. The low-grade inflammation persists even after reversing pro-inflammatory stimuli such as LDL cholesterol and the renin–angiotensin system (RAS. Recently, several possible sources of chronic low-grade inflammation observed during aging and age-related diseases have been proposed. Cell senescence and dysregulation of innate immunity is one such mechanism by which persistent prolonged inflammation occurs even after the initial stimulus has been removed. Additionally, the coagulation factor that activates inflammatory signaling beyond its role in the coagulation system has been identified. This signal could be a new source of chronic inflammation and cell senescence. Here, we summarized the factors and cellular pathways/processes that are known to regulate low-grade persistent inflammation in aging and age-related disease.

  3. [COPD and inflammation: statement from a French expert group. Phenotypes related to inflammation].

    Science.gov (United States)

    Perez, T; Mal, H; Aguilaniu, B; Brillet, P-Y; Chaouat, A; Louis, R; Muir, J-F; Similowski, T; Berger, P; Burgel, P-R; Chambellan, A; Chanez, P; Devillier, P; Escamilla, R; Marthan, R; Wallaert, B; Aubier, M; Roche, N

    2011-02-01

    The objective of the present article is to review available data on possible links between phenotypes and inflammatory profiles in patients with chronic obstructive pulmonary disease (COPD). Chronic bronchitis is associated with proximal bronchial inflammation and small airway inflammation with remodeling at the site of obstruction. CT scanning enables patients to be phenotyped according to the predominantly bronchial or emphysematous nature of the morphological abnormality. Exacerbations, in a context of persistently elevated baseline inflammation, are associated with increased inflammation and a poor prognosis. Long-term studies have correlated inflammatory markers (and anti-inflammatory drug effects) with dynamic hyperinflation, possibly confirming that inflammation promotes hyperinflation. The inflammatory cell count in the pulmonary arterial walls correlates with the severity of endothelial dysfunction. The risk of developing pulmonary hypertension would seem to increase with low-grade systemic inflammation. The role of low-grade systemic inflammation in COPD co-morbidities, and in nutritional and muscular involvement in particular, remains a matter of debate. Regular physical exercise may help reduce this inflammation. In COPD, many aspects of the clinical phenotype are related to inflammation. Better knowledge of these relationships could help optimize current and future treatments. Copyright © 2011. Published by Elsevier Masson SAS.

  4. Interleukin 32, inflammation and cancer.

    Science.gov (United States)

    Hong, Jin Tae; Son, Dong Ju; Lee, Chong Kil; Yoon, Do-Young; Lee, Dong Hun; Park, Mi Hee

    2017-06-01

    Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. IL-32 gene consists of eight small exons, and IL-32 mRNA has nine alternative spliced isoforms, and was thought to be secreted because it contains an internal signal sequence and lacks a transmembrane region. IL-32 is initially expressed selectively in activated T cells by mitogen and activated NK cells and their expression is strongly augmented by microbes, mitogens, and other cytokines. The IL-32 is induced mainly by pathogens and pro-inflammatory cytokines, but IL-32 is more prominent in immune cells than in non-immune tissues. The IL-32 transcript is expressed in various human tissues and organs such as the spleen, thymus, leukocyte, lung, small intestine, colon, prostate, heart, placenta, liver, muscle, kidney, pancreas, and brain. Cytokines are critical components of cell signaling pathways that are involved in the regulation of cell growth, metabolism, hormone signaling, immune regulation and a variety of other physiological functions. Earlier studies have demonstrated that IL-32 regulates cell growth, metabolism and immune regulation and is therefore involved in the pathologic regulator or protectant of inflammatory diseases. Previous studies defined that IL-32 is upregulated in the patients with several inflammatory diseases, and is induced by inflammatory responses. However, several reports suggested that IL-32 is downregulated in several inflammatory diseases including asthma, HIV infection disease, neuronal diseases, metabolic disorders, experimental colitis and metabolic disorders. IL-32 is also involved in various cancer malignancies including renal cancer, esophageal cancer and hepatocellular carcinoma, lung cancer, gastric cancer, breast cancer, pancreatic cancer, lymphoma, osteosarcoma, breast cancer, colon cancer and thyroid carcinoma. Other studies suggested that IL-32 decreases tumor development including cervical cancer, colon cancer and prostate cancer

  5. Cerebellar white matter inflammation and demyelination in chronic relapsing experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Wanscher, B.; Sørensen, P. S.; Juhler, M.

    1993-01-01

    Experimental allergic encephalomyelitis, demyelination, inflammation, immunology, neuropathology......Experimental allergic encephalomyelitis, demyelination, inflammation, immunology, neuropathology...

  6. Adipose Tissue Remodeling as Homeostatic Inflammation

    Directory of Open Access Journals (Sweden)

    Michiko Itoh

    2011-01-01

    Full Text Available Evidence has accumulated indicating that obesity is associated with a state of chronic, low-grade inflammation. Obese adipose tissue is characterized by dynamic changes in cellular composition and function, which may be referred to as “adipose tissue remodeling”. Among stromal cells in the adipose tissue, infiltrated macrophages play an important role in adipose tissue inflammation and systemic insulin resistance. We have demonstrated that a paracrine loop involving saturated fatty acids and tumor necrosis factor-α derived from adipocytes and macrophages, respectively, aggravates obesity-induced adipose tissue inflammation. Notably, saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced lipolysis, serve as a naturally occurring ligand for Toll-like receptor 4 complex, thereby activating macrophages. Such a sustained interaction between endogenous ligands derived from parenchymal cells and pathogen sensors expressed in stromal immune cells should lead to chronic inflammatory responses ranging from the basal homeostatic state to diseased tissue remodeling, which may be referred to as “homeostatic inflammation”. We, therefore, postulate that adipose tissue remodeling may represent a prototypic example of homeostatic inflammation. Understanding the molecular mechanism underlying homeostatic inflammation may lead to the identification of novel therapeutic strategies to prevent or treat obesity-related complications.

  7. Asthma, GERD and Obesity: Triangle of Inflammation.

    Science.gov (United States)

    Gupta, Samriti; Lodha, Rakesh; Kabra, S K

    2017-11-11

    There is increasing prevalence of both asthma and obesity in children globally in recent years. Various epidemiological studies link obesity as a risk factor for asthma and suggest a possible causal association. Obesity asthma phenotype is considered as distinct in view of greater severity and poor asthma control. Various mechanisms underlying this phenotype have been suggested including mechanical effects of obesity and systemic inflammation, but still the exact mechanism is unclear. Also, the comorbidities like gastroesophageal reflux disease (GERD) and sleep disordered breathing (SDB) lead to inflammation in airways and contribute to asthma obesity association. A better understanding of mechanisms by which obesity and GERD lead to inflammation in airways and increase the risk of asthma may provide insight towards targeted treatment approach of these patients.

  8. Adiponectin and leptin: new targets in inflammation.

    Science.gov (United States)

    Scotece, Morena; Conde, Javier; López, Verónica; Lago, Francisca; Pino, Jesús; Gómez-Reino, Juan Jesús; Gualillo, Oreste

    2014-01-01

    Inflammation is a complex mechanism of cell/tissue responses to injuries triggered by multiple causes, including trauma, pathogens or autoimmune abnormal responses. In the last years, a novel line of thought is emerging by giving a more holistic vision of chronic arthropathies through a recently identified group of molecules, called adipokines. Actually, most of these recently identified factors, produced prevalently by white adipose tissue but also by cells of the joints (chondrocytes and synovial fibroblasts) and immune cells, play a significant role in chronic inflammation. Adipokines dysregulation has emerged as a common characteristic of chronic inflammation in rheumatic diseases in particular when obesity or, more precisely, adipose tissue dysfunction is associated with common rheumatic diseases, such as osteoarthritis and rheumatoid arthritis. In this MiniReview, we discuss the role of adipokines in osteoarthritis and rheumatoid arthritis providing an updated overview of their pathophysiological role and potential use as therapeutic targets. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

  9. The AT2 Receptor and Inflammation

    DEFF Research Database (Denmark)

    Esquitino, Veronica Valero; Danyel, Leon Alexander; Steckelings, Ulrike M.

    2015-01-01

    This chapter summarizes current knowledge about the role of the angiotensin type 2 (AT2) receptor in inflammation. The first section provides an overview about molecular mechanisms underlying the anti-inflammatory action of the AT2 receptor. This section is followed by a rev......This chapter summarizes current knowledge about the role of the angiotensin type 2 (AT2) receptor in inflammation. The first section provides an overview about molecular mechanisms underlying the anti-inflammatory action of the AT2 receptor. This section is followed...... by a review of the existing literature addressing the role of the AT2 receptor in a wide range of disorders, in which acute or chronic inflammation is an essential contributor to the pathology. These disorders comprise cardiovascular, cerebrovascular, renal, and autoimmune diseases.Taken as a whole...

  10. The role of prolactin in prostatic inflammation

    Directory of Open Access Journals (Sweden)

    Edson João da Silva

    2013-12-01

    Full Text Available Several reports have shown that prolactin (PRL plays a role in prostatic growth, but few studies considered the role of PRL in the process of prostatic inflammation. Young (45 ± 5 days old and adult (75 ± 5 days old male Wistar rats were subcutaneously injected daily with domperidone (4.0 mg.kg-1 to maintain high serum PRL levels. The animals were treated for 15, 30, 45 or 60 days. Blood and prostate samples were collected at the end of each treatment for PRL dosage and histological analysis, respectively. Only young animals treated with DOMP for 15 and 30 days displayed inflammatory infiltrate in the prostate. These results confirm literature data in regards to PRL involvement in inducing prostate inflammation. Moreover, it was concluded that young animals are more susceptible then adults to the PRL action concerning prostate inflammation.

  11. Neurobiology of inflammation-associated anorexia

    Directory of Open Access Journals (Sweden)

    Laurent Gautron

    2010-01-01

    Full Text Available Compelling data demonstrate that inflammation-associated anorexia directly results from the action of pro-inflammatory factors, primarily cytokines and prostaglandins E2, on the nervous system. For instance, the aforementioned pro-inflammatory factors can stimulate the activity of peripheral sensory neurons, and induce their own de novo synthesis and release into the brain parenchyma and cerebrospinal fluid. Ultimately, it results in the mobilization of a specific neural circuit that shuts down appetite. The present article describes the different cell groups and neurotransmitters involved in inflammation-associated anorexia and examines how they interact with neural systems regulating feeding such as the melanocortin system. A better understanding of the neurobiological mechanisms underlying inflammation-associated anorexia will help to develop appetite stimulants for cancer and AIDS patients.

  12. Curbing Inflammation in hemorrhagic trauma: a review

    Directory of Open Access Journals (Sweden)

    MAURICIO GODINHO

    Full Text Available Trauma is one of the world's leading causes of death within the first 40 years of life and thus a significant health problem. Trauma accounts for nearly a third of the lost years of productive life before 65 years of age and is associated with infection, hemorrhagic shock, reperfusion syndrome, and inflammation. The control of hemorrhage, coagulopathy, optimal use of blood products, balancing hypo and hyperperfusion, and hemostatic resuscitation improve survival in cases of trauma with massive hemorrhage. This review discusses inflammation in the context of trauma-associated hemorrhagic shock. When one considers the known immunomodulatory effects of traumatic injury, allogeneic blood transfusion, and the overlap between patient populations, it is surprising that so few studies have assessed their combined effects on immune function. We also discuss the relative benefits of curbing inflammation rather than attempting to prevent it.

  13. Inflammation Is Associated with Voriconazole Trough Concentrations

    Science.gov (United States)

    van Wanrooy, Marjolijn J. P.; Span, Lambert F. R.; Rodgers, Michael G. G.; van den Heuvel, Edwin R.; Uges, Donald R. A.; van der Werf, Tjip S.; Kosterink, Jos G. W.

    2014-01-01

    Voriconazole concentrations display a large variability, which cannot completely be explained by known factors. Inflammation may be a contributing factor, as inflammatory stimuli can change the activities and expression levels of cytochrome P450 isoenzymes. We explored the correlation between inflammation, reflected by C-reactive protein (CRP) concentrations, and voriconazole trough concentrations. A retrospective chart review of patients with at least one steady-state voriconazole trough concentration and a CRP concentration measured on the same day was performed. A total of 128 patients were included. A significantly (P voriconazole trough concentration was observed in patients with severe inflammation (6.2 mg/liter; interquartile range [IQR], 3.4 to 8.7 mg/liter; n = 20) than in patients with moderate inflammation (3.4 mg/liter; IQR, 1.6 to 5.4 mg/liter; n = 60) and in patients with no to mild inflammation (1.6 mg/liter; IQR, 0.8 to 3.0 mg/liter; n = 48). The patients in all three groups received similar voriconazole doses based on mg/kg body weight (P = 0.368). Linear regression analyses, both unadjusted and adjusted for covariates of gender, age, dose, route of administration, liver enzymes, and interacting coadministered medications, showed a significant association between voriconazole and CRP concentration (P voriconazole trough concentration increased by 0.015 mg/liter (unadjusted 95% confidence interval [CI], 0.011 to 0.020 mg/liter; adjusted 95% CI, 0.011 to 0.019 mg/liter). Inflammation, reflected by the C-reactive protein concentration, is associated with voriconazole trough concentrations. Further research is necessary to assess if taking the inflammatory status of a patient into account is helpful in therapeutic drug monitoring of voriconazole to maintain concentrations in the therapeutic window, thereby possibly preventing suboptimal treatment or adverse events. PMID:25223994

  14. Anesthetics Impact the Resolution of Inflammation

    Science.gov (United States)

    Fredman, Gabrielle; Kasuga, Kie; Gelman, Simon; Serhan, Charles N.

    2008-01-01

    Background Local and volatile anesthetics are widely used for surgery. It is not known whether anesthetics impinge on the orchestrated events in spontaneous resolution of acute inflammation. Here we investigated whether a commonly used local anesthetic (lidocaine) and a widely used inhaled anesthetic (isoflurane) impact the active process of resolution of inflammation. Methods and Findings Using murine peritonitis induced by zymosan and a systems approach, we report that lidocaine delayed and blocked key events in resolution of inflammation. Lidocaine inhibited both PMN apoptosis and macrophage uptake of apoptotic PMN, events that contributed to impaired PMN removal from exudates and thereby delayed the onset of resolution of acute inflammation and return to homeostasis. Lidocaine did not alter the levels of specific lipid mediators, including pro-inflammatory leukotriene B4, prostaglandin E2 and anti-inflammatory lipoxin A4, in the cell-free peritoneal lavages. Addition of a lipoxin A4 stable analog, partially rescued lidocaine-delayed resolution of inflammation. To identify protein components underlying lidocaine's actions in resolution, systematic proteomics was carried out using nanospray-liquid chromatography-tandem mass spectrometry. Lidocaine selectively up-regulated pro-inflammatory proteins including S100A8/9 and CRAMP/LL-37, and down-regulated anti-inflammatory and some pro-resolution peptides and proteins including IL-4, IL-13, TGF-â and Galectin-1. In contrast, the volatile anesthetic isoflurane promoted resolution in this system, diminishing the amplitude of PMN infiltration and shortening the resolution interval (Ri) ∼50%. In addition, isoflurane down-regulated a panel of pro-inflammatory chemokines and cytokines, as well as proteins known to be active in cell migration and chemotaxis (i.e., CRAMP and cofilin-1). The distinct impact of lidocaine and isoflurane on selective molecules may underlie their opposite actions in resolution of inflammation

  15. Anesthetics impact the resolution of inflammation.

    Directory of Open Access Journals (Sweden)

    Nan Chiang

    2008-04-01

    Full Text Available Local and volatile anesthetics are widely used for surgery. It is not known whether anesthetics impinge on the orchestrated events in spontaneous resolution of acute inflammation. Here we investigated whether a commonly used local anesthetic (lidocaine and a widely used inhaled anesthetic (isoflurane impact the active process of resolution of inflammation.Using murine peritonitis induced by zymosan and a systems approach, we report that lidocaine delayed and blocked key events in resolution of inflammation. Lidocaine inhibited both PMN apoptosis and macrophage uptake of apoptotic PMN, events that contributed to impaired PMN removal from exudates and thereby delayed the onset of resolution of acute inflammation and return to homeostasis. Lidocaine did not alter the levels of specific lipid mediators, including pro-inflammatory leukotriene B(4, prostaglandin E(2 and anti-inflammatory lipoxin A(4, in the cell-free peritoneal lavages. Addition of a lipoxin A(4 stable analog, partially rescued lidocaine-delayed resolution of inflammation. To identify protein components underlying lidocaine's actions in resolution, systematic proteomics was carried out using nanospray-liquid chromatography-tandem mass spectrometry. Lidocaine selectively up-regulated pro-inflammatory proteins including S100A8/9 and CRAMP/LL-37, and down-regulated anti-inflammatory and some pro-resolution peptides and proteins including IL-4, IL-13, TGF-â and Galectin-1. In contrast, the volatile anesthetic isoflurane promoted resolution in this system, diminishing the amplitude of PMN infiltration and shortening the resolution interval (Ri approximately 50%. In addition, isoflurane down-regulated a panel of pro-inflammatory chemokines and cytokines, as well as proteins known to be active in cell migration and chemotaxis (i.e., CRAMP and cofilin-1. The distinct impact of lidocaine and isoflurane on selective molecules may underlie their opposite actions in resolution of inflammation

  16. Kost, diabetes mellitus og parodontal inflammation

    DEFF Research Database (Denmark)

    Damgaard, Christian; Holmstrup, Palle

    2017-01-01

    Nærværende artikel præsenterer en oversigt over den foreliggende viden om kostens betydning for diabetes mellitus (DM) og parodontal inflammation. Der er i vekslende grad dokumentation for sammenhænge mellem kost, DM og marginal parodontitis (MP). Med baggrund i forøget viden om kostens betydning...... for udviklingen af henholdsvis DM og parodontal inflammation bør tandlæger også rådgive om kost for derigennem at styrke behandlingen af patienter med MP og DM....

  17. Preoperative ultraviolet B inflammation in skin

    DEFF Research Database (Denmark)

    Lunn, T H; Dawes, J M; Denk, F

    2018-01-01

    and transcriptional analysis of hyperalgesia arising as a result of UVB-induced inflammation in patients before total knee arthroplasty (TKA, n = 23). Levels of acute postoperative pain were assessed and correlated with preoperative data. RESULTS: Cytokine and chemokine responses after UVB irradiation were found...... to be inversely correlated with the level of pain experienced after surgery (Spearman's ρ = -0.498). CONCLUSION: It may be possible to use this simple model to study and predict the nature of neuro-immune responses at more remote, clinically relevant sites. SIGNIFICANCE: A simple model of UVB inflammation...

  18. Kost, diabetes mellitus og parodontal inflammation

    DEFF Research Database (Denmark)

    Damgaard, Christian; Holmstrup, Palle

    2016-01-01

    Nærværende artikel præsenterer en oversigt over den foreliggende viden om kostens betydning for diabetes mellitus (DM) og parodontal inflammation. Der er i vekslende grad dokumentation for sammenhænge mellem kost, DM og marginal parodontitis (MP). Med baggrund i forøget viden om kostens betydning...... for udviklingen af henholdsvis DM og parodontal inflammation bør tandlæger også rådgive om kost for derigennem at styrke behandlingen af patienter med MP og DM....

  19. Nuklearmedicinske teknikker: diagnostik af inflammation og infektion

    DEFF Research Database (Denmark)

    Alstrup, Aage Kristian Olsen; Afzelius, Pia

    2017-01-01

    Knogleskintigrafi har vundet indpas i veterinær hestepraksis, hvor undersøgelsen primært anvendes til halthedsdiagnostik, mens de øvrige teknikker til diagnostik af inflammation og infektioner kun er i deres vorden i veterinær praksis.......Knogleskintigrafi har vundet indpas i veterinær hestepraksis, hvor undersøgelsen primært anvendes til halthedsdiagnostik, mens de øvrige teknikker til diagnostik af inflammation og infektioner kun er i deres vorden i veterinær praksis....

  20. Inflammation-induced lymphangiogenesis and lymphatic dysfunction

    Science.gov (United States)

    Liao, Shan; von der Weid, Pierre-Yves

    2014-01-01

    The lymphatic system is intimately linked to tissue fluid homeostasis and immune cell trafficking. These functions are paramount in the establishment and development of an inflammatory response. In the past decade, an increasing number of reports has revealed that marked changes, such as lymphangiogenesis and lymphatic contractile dysfunction occur in both vascular and nodal parts of the lymphatic system during inflammation, as well as other disease processes. This review provides a critical update on the role of the lymphatic system in disease process such as chronic inflammation and cancer and examines the changes in lymphatic functions the diseases cause and the influence these changes have on the progression of the diseases. PMID:24449090

  1. Adipose Tissue Inflammation Induces B Cell Inflammation and Decreases B Cell Function in Aging

    Directory of Open Access Journals (Sweden)

    Daniela Frasca

    2017-08-01

    Full Text Available Aging is the greatest risk factor for developing chronic diseases. Inflamm-aging, the age-related increase in low-grade chronic inflammation, may be a common link in age-related diseases. This review summarizes recent published data on potential cellular and molecular mechanisms of the age-related increase in inflammation, and how these contribute to decreased humoral immune responses in aged mice and humans. Briefly, we cover how aging and related inflammation decrease antibody responses in mice and humans, and how obesity contributes to the mechanisms for aging through increased inflammation. We also report data in the literature showing adipose tissue infiltration with immune cells and how these cells are recruited and contribute to local and systemic inflammation. We show that several types of immune cells infiltrate the adipose tissue and these include macrophages, neutrophils, NK cells, innate lymphoid cells, eosinophils, T cells, B1, and B2 cells. Our main focus is how the adipose tissue affects immune responses, in particular B cell responses and antibody production. The role of leptin in generating inflammation and decreased B cell responses is also discussed. We report data published by us and by other groups showing that the adipose tissue generates pro-inflammatory B cell subsets which induce pro-inflammatory T cells, promote insulin resistance, and secrete pathogenic autoimmune antibodies.

  2. Exercise alleviates depression related systemic inflammation in ...

    African Journals Online (AJOL)

    Background: Depression is a highly prevalent co-morbidity in Chronic Obstructive Pulmonary Disease (COPD) which was shown to be ... Conclusion: Aerobic exercise is an effective treatment policy to improve depression related to systemic inflammation in patients ... serotonin reuptake inhibitor) for the treatment of depres-.

  3. Genes, inflammation, and age-related diseases

    NARCIS (Netherlands)

    Trompet, Stella

    2010-01-01

    The general objective of this thesis was to investigate associations between genetic variants involved in inflammation and epigenetics and age-related diseases in an elderly cohort to get more insights in the patho-physiological mechanisms involved in age-related diseases, like cardiovascular

  4. Infection, inflammation and exercise in cystic fibrosis

    Science.gov (United States)

    2013-01-01

    Regular exercise is positively associated with health. It has also been suggested to exert anti-inflammatory effects. In healthy subjects, a single exercise session results in immune cell activation, which is characterized by production of immune modulatory peptides (e.g. IL-6, IL-8), a leukocytosis and enhanced immune cell functions. Upon cessation of exercise, immune activation is followed by a tolerizing phase, characterized by a reduced responsiveness of immune cells. Regular exercise of moderate intensity and duration has been shown to exert anti-inflammatory effects and is associated with a reduced disease incidence and viral infection susceptibility. Specific exercise programs may therefore be used to modify the course of chronic inflammatory and infectious diseases such as cystic fibrosis (CF). Patients with CF suffer from severe and chronic pulmonary infections and inflammation, leading to obstructive and restrictive pulmonary disease, exercise intolerance and muscle cachexia. Inflammation is characterized by a hyper-inflammatory phenotype. Patients are encouraged to engage in exercise programs to maintain physical fitness, quality of life, pulmonary function and health. In this review, we present an overview of available literature describing the association between regular exercise, inflammation and infection susceptibility and discuss the implications of these observations for prevention and treatment of inflammation and infection susceptibility in patients with CF. PMID:23497303

  5. lipid profile, hyperglycaemia, systemic inflammation and ...

    African Journals Online (AJOL)

    user

    Introduction: The aim of this study was to estimate the mean prevalence of dyslipidaemia, hyperglycaemia, systemic inflammation and anthropometry as CVD risk factors as well as dietary intakes and to investigate associations between these CVD risk factors and dietary intakes among apparently healthy school-aged.

  6. Salivary cytokine levels in early gingival inflammation

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Damgaard, Christian; Könönen, Eija

    2017-01-01

    Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte chemoattr......Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte...... chemoattractant protein (MCP)-1, IL-1β, and IL-1 receptor antagonist (IL-1Ra) in gingival inflammation. Twenty-eight systemically and orally healthy nonsmokers abstained from oral hygiene protocols for 10 days. After that, self-performed cleaning was resumed for 14 days. Plaque and gingival indexes were measured...... levels decreased and remained low during development and resolution of experimental gingivitis. Initial inflammation in gingival tissues is associated with a decrease in inflammatory cytokines in saliva. Further studies are needed to evaluate if inflammatory cytokines bind to their functional receptors...

  7. Pleiotropic genes for metabolic syndrome and inflammation

    DEFF Research Database (Denmark)

    Kraja, Aldi T; Chasman, Daniel I; North, Kari E

    2014-01-01

    , PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional...

  8. Airway inflammation in mild cystic fibrosis.

    Science.gov (United States)

    Eckrich, Jonas; Zissler, Ulrich M; Serve, Friederike; Leutz, Patricia; Smaczny, Christina; Schmitt-Grohé, Sabina; Fussbroich, Daniela; Schubert, Ralf; Zielen, Stefan; Eickmeier, Olaf

    2017-01-01

    Airway infection and inflammation play major roles in the progression of cystic fibrosis (CF) lung disease. In patients with mild disease, airway inflammation is a clinically relevant and often underdiagnosed feature. Lung function, sputum cell counts, and cytokine profiles in CF with mild disease might be different in patients with and without involvement of small airway disease (SAD). Patients with mild CF (n=32) and 22 healthy controls were enrolled in this study. Patients with CF were assigned to two groups: (1) patients without SAD (n=19, median age 12.3years, MEF 25 >50% predicted), and (2) patients with SAD (n=13 median age, 13.2years, MEF 25 inflammation compared to controls as indicated by elevated levels of sputum biomarkers like total cells, neutrophils, and IL6. Our study demonstrated that patients with CF with mild disease defined by lung function might be further endotyped according to their involvement of SAD. In patients with CF and SAD, airway neutrophilic inflammation is more pronounced and is in part distinct from that seen in patients without SAD. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  9. Kost, diabetes mellitus og parodontal inflammation

    DEFF Research Database (Denmark)

    Damgaard, Christian; Holmstrup, Palle

    2017-01-01

    Nærværende artikel præsenterer en oversigt over den foreliggende viden om kostens betydning for diabetes mellitus (DM) og parodontal inflammation. Der er i vekslende grad dokumentation for sammenhænge mellem kost, DM og marginal parodontitis (MP). Med baggrund i forøget viden om kostens betydning...

  10. Inflammation and fertility in the mare

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Troedsson, Mats H.T.

    2017-01-01

    -inflammatory factors is required for resolving the breeding-induced inflammation within 24–36 hr in the reproductively healthy mare, whereas a subpopulation of mares is susceptible to development of a persistent infection that can interfere with fertility. The aetiology of persistent endometritis can be either...

  11. Innate lymphoid cells in inflammation and immunity

    NARCIS (Netherlands)

    McKenzie, Andrew N. J.; Spits, Hergen; Eberl, Gerard

    2014-01-01

    Innate lymphoid cells (ILCs) were first described as playing important roles in the development of lymphoid tissues and more recently in the initiation of inflammation at barrier surfaces in response to infection or tissue damage. It has now become apparent that ILCs play more complex roles

  12. Hyperglycemia and Inflammation in older individuals.

    NARCIS (Netherlands)

    de Rekeneire, N.; Peila, R.; Ding, J.; Colbert, L.H.; Visser, M.; Shorr, R.I.; Kritchevsky, S.B.; Kuller, L.H.; Strotmeyer, E.M.; Schwartz, A.V.; Vellas, B.; Harris, T.B.

    2006-01-01

    OBJECTIVE - The objective of this study was to assess the association of inflammation with hyperglycemia (impaired fasting glucose [IFG]/impaired glucose tolerance [IGT]) and diabetes in older individuals. RESEARCH DESIGN AND METHODS - Baseline data from the Health, Aging and Body Composition study

  13. Regulation of inflammation in Japanese encephalitis.

    Science.gov (United States)

    Lannes, Nils; Summerfield, Artur; Filgueira, Luis

    2017-08-14

    Uncontrolled inflammatory response of the central nervous system is a hallmark of severe Japanese encephalitis (JE). Although inflammation is necessary to mount an efficient immune response against virus infections, exacerbated inflammatory response is often detrimental. In this context, cells of the monocytic lineage appear to be important forces driving JE pathogenesis. Brain-infiltrating monocytes, macrophages and microglia play a major role in central nervous system (CNS) inflammation during JE. Moreover, the role of inflammatory monocytes in viral neuroinvasion during JE and mechanisms of cell entry into the CNS remains unclear. The identification of cellular and molecular actors in JE inflammatory responses may help to understand the mechanisms behind excessive inflammation and to develop therapeutics to treat JE patients. This review addresses the current knowledge about mechanisms of virus neuroinvasion, neuroinflammation and therapeutics critical for JE outcome. Understanding the regulation of inflammation in JE is challenging. Elucidation of the remaining open questions will help to the development of therapeutic approaches avoiding detrimental inflammatory responses in JE.

  14. Measuring fire weather and forest inflammability

    Science.gov (United States)

    H. T. Gisborne

    1936-01-01

    In the measurement of fire weather and forest inflammability, now practiced regularly at more than 90 forest stations in northern Idaho and western Montana, it is necessary to use many methods that are peculiar to this work. Some of these methods are familiar to meteorologists, but few foresters have had any appreciable training in meteorology. Others are of such,...

  15. Epoxygenated Fatty Acids Inhibit Retinal Vascular Inflammation.

    Science.gov (United States)

    Capozzi, Megan E; Hammer, Sandra S; McCollum, Gary W; Penn, John S

    2016-12-14

    The objective of the present study was to assess the effect of elevating epoxygenated fatty acids on retinal vascular inflammation. To stimulate inflammation we utilized TNFα, a potent pro-inflammatory mediator that is elevated in the serum and vitreous of diabetic patients. In TNFα-stimulated primary human retinal microvascular endothelial cells, total levels of epoxyeicosatrienoic acids (EETs), but not epoxydocosapentaenoic acids (EDPs), were significantly decreased. Exogenous addition of 11,12-EET or 19,20-EDP when combined with 12-(3-adamantane-1-yl-ureido)-dodecanoic acid (AUDA), an inhibitor of epoxide hydrolysis, inhibited VCAM-1 and ICAM-1 expression and protein levels; conversely the diol product of 19,20-EDP hydrolysis, 19,20-DHDP, induced VCAM1 and ICAM1 expression. 11,12-EET and 19,20-EDP also inhibited leukocyte adherence to human retinal microvascular endothelial cell monolayers and leukostasis in an acute mouse model of retinal inflammation. Our results indicate that this inhibition may be mediated through an indirect effect on NFκB activation. This is the first study demonstrating a direct comparison of EET and EDP on vascular inflammatory endpoints, and we have confirmed a comparable efficacy from each isomer, suggesting a similar mechanism of action. Taken together, these data establish that epoxygenated fatty acid elevation will inhibit early pathology related to TNFα-induced inflammation in retinal vascular diseases.

  16. Dietary Anthocyanins against Obesity and Inflammation

    Directory of Open Access Journals (Sweden)

    Yoon-Mi Lee

    2017-10-01

    Full Text Available Chronic low-grade inflammation plays a pivotal role in the pathogenesis of obesity, due to its associated chronic diseases such as type II diabetes, cardiovascular diseases, pulmonary diseases and cancer. Thus, targeting inflammation is an attractive strategy to counter the burden of obesity-induced health problems. Recently, food-derived bioactive compounds have been spotlighted as a regulator against various chronic diseases due to their low toxicity, as opposed to drugs that induce severe side effects. Here we describe the beneficial effects of dietary anthocyanins on obesity-induced metabolic disorders and inflammation. Red cabbage microgreen, blueberry, blackcurrant, mulberry, cherry, black elderberry, black soybean, chokeberry and jaboticaba peel contain a variety of anthocyanins including cyanidins, delphinidins, malvidins, pelargonidins, peonidins and petunidins, and have been reported to alter both metabolic markers and inflammatory markers in cells, animals, and humans. This review discusses the interplay between inflammation and obesity, and their subsequent regulation via the use of dietary anthocyanins, suggesting an alternative dietary strategy to ameliorate obesity and obesity associated chronic diseases.

  17. Evidence for Inflammation-Associated Depression.

    Science.gov (United States)

    Liu, Celina S; Adibfar, Alexander; Herrmann, Nathan; Gallagher, Damien; Lanctôt, Krista L

    This chapter explores the evidence supporting inflammation-associated depression. Data to date suggest a bidirectional relationship between inflammation and depression wherein one process can drive the other. A wealth of animal and clinical studies have demonstrated an association between concentrations of pro-inflammatory cytokines - specifically interleukin (IL)-1β, IL-6, and tumor necrosis factor-α - and depressive symptoms. There is also evidence that this pro-inflammatory state is accompanied by aberrant inflammation-related processes including platelet activation factor hyperactivity, oxidative and nitrosative stress, and damage to mitochondria. These complex and interrelated mechanisms can collectively contribute to negative neurobiological outcomes that may, in part, underlie the etiopathology of depression. Mounting evidence has shown a concomitant reduction in both depressive symptoms and pro-inflammatory cytokine concentrations following treatment with pharmacological anti-inflammatory interventions. Taken together, the reviewed preclinical and clinical findings may suggest the existence of a distinct inflammatory subtype of depression in which these patients exhibit unique biochemical and clinical features and may potentially experience improved clinical outcomes with inflammation-targeted pharmacotherapy.

  18. A data-driven acute inflammation therapy.

    Science.gov (United States)

    Radosavljevic, Vladan; Ristovski, Kosta; Obradovic, Zoran

    2013-01-01

    Acute inflammation is a severe medical condition defined as an inflammatory response of the body to an infection. Its rapid progression requires quick and accurate decisions from clinicians. Inadequate and delayed decisions makes acute inflammation the 10th leading cause of death overall in United States with the estimated cost of treatment about $17 billion annually. However, despite the need, there are limited number of methods that could assist clinicians to determine optimal therapies for acute inflammation. We developed a data-driven method for suggesting optimal therapy by using machine learning model that is learned on historical patients' behaviors. To reduce both the risk of failure and the expense for clinical trials, our method is evaluated on a virtual patients generated by a mathematical model that emulates inflammatory response. In conducted experiments, acute inflammation was handled with two complimentary pro- and anti-inflammatory medications which adequate timing and doses are crucial for the successful outcome. Our experiments show that the dosage regimen assigned with our data-driven method significantly improves the percentage of healthy patients when compared to results by other methods used in clinical practice and found in literature. Our method saved 88% of patients that would otherwise die within a week, while the best method found in literature saved only 73% of patients. At the same time, our method used lower doses of medications than alternatives. In addition, our method achieved better results than alternatives when only incomplete or noisy measurements were available over time as well as it was less affected by therapy delay. The presented results provide strong evidence that models from the artificial intelligence community have a potential for development of personalized treatment strategies for acute inflammation.

  19. Role of Smooth Muscle in Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Stephen M Collins

    1996-01-01

    Full Text Available The notion that smooth muscle function is altered in inflammation is prompted by clinical observations of altered motility in patients with inflammatory bowel disease (IBD. While altered motility may reflect inflammation-induced changes in intrinsic or extrinsic nerves to the gut, changes in gut hormone release and changes in muscle function, recent studies have provided in vitro evidence of altered muscle contractility in muscle resected from patients with ulcerative colitis or Crohn’s disease. In addition, the observation that smooth muscle cells are more numerous and prominent in the strictured bowel of IBD patients compared with controls suggests that inflammation may alter the growth of intestinal smooth muscle. Thus, inflammation is associated with changes in smooth muscle growth and contractility that, in turn, contribute to important symptoms of IBD including diarrhea (from altered motility and pain (via either altered motility or stricture formation. The involvement of smooth muscle in this context may be as an innocent bystander, where cells and products of the inflammatory process induce alterations in muscle contractility and growth. However, it is likely that intestinal muscle cells play a more active role in the inflammatory process via the elaboration of mediators and trophic factors, including cytokines, and via the production of collagen. The concept of muscle cells as active participants in the intestinal inflammatory process is a new concept that is under intense study. This report summarizes current knowledge as it relates to these two aspects of altered muscle function (growth and contractility in the inflamed intestine, and will focus on mechanisms underlying these changes, based on data obtained from animal models of intestinal inflammation.

  20. Lipoxins: nature's way to resolve inflammation

    Directory of Open Access Journals (Sweden)

    Chandrasekharan JA

    2015-09-01

    Full Text Available Jayashree A Chandrasekharan, Neelam Sharma-Walia HM Bligh Cancer Research Laboratories, Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USAAbstract: An effective host defense mechanism involves inflammation to eliminate pathogens from the site of infection, followed by the resolution of inflammation and the restoration of tissue homeostasis. Lipoxins are endogenous anti-inflammatory, pro-resolving molecules that play a vital role in reducing excessive tissue injury and chronic inflammation. In this review, the mechanisms of action of lipoxins at the site of inflammation and their interaction with other cellular signaling molecules and transcription factors are discussed. Emphasis has also been placed on immune modulatory role(s of lipoxins. Lipoxins regulate components of both the innate and adaptive immune systems including neutrophils, macrophages, T-, and B-cells. Lipoxins also modulate levels of various transcription factors such as nuclear factor κB, activator protein-1, nerve growth factor-regulated factor 1A binding protein 1, and peroxisome proliferator activated receptor γ and control the expression of many inflammatory genes. Since lipoxins and aspirin-triggered lipoxins have clinical relevance, we discuss their important role in clinical research to treat a wide range of diseases like inflammatory disorders, renal fibrosis, cerebral ischemia, and cancer. A brief overview of lipoxins in viral malignancies and viral pathogenesis especially the unexplored role of lipoxins in Kaposi's sarcoma-associated herpes virus biology is also presented. Keywords: lipoxins, epi-lipoxins, inflammation, pro-resolving, aspirin-triggered lipoxins, cyclooxygenases, lipoxygenases, therapeutic potential, transcription factors, Kaposi's sarcoma-associated herpes virus

  1. Melanin: A scavenger in gingival inflammation

    Directory of Open Access Journals (Sweden)

    S Nilima

    2011-01-01

    Full Text Available Background: One of the major direct or indirect targets of ultraviolet exposure of skin is the melanocyte or the melanin -forming cell. Epidermal melanocytes act as a trap for free radicals. Based on the protective role of melanocytes in medical literature, the role of melanin pigmentation in gingiva needs to be elucidated. Periodontal pathogens and their products demonstrate the ability to induce the generation of reactive oxygen species. Hence purpose of this study was to unravel the protective role of melanin (if any against the gingival inflammation. Materials and Methods: A total of 80 subjects; 20 in each group were selected. The selection of subjects regarding gingival pigmentation was based on Dummett′s scoring criteria 0, 3. A complete medical, dental history and an informed consent were obtained from the patients. After evaluation of clinical parameters the GCF was collected using microcapillary pipettes at the selected sites. IL-1β levels were quantitated using ELISA. Results: In non-pigmented healthy and gingivitis groups, there was a positive correlation between plaque index, gingival index and bleeding index versus IL-1β level: indicating an increase in the biochemical mediator of inflammation corresponding to an increase in the clinical parameters of inflammation. Also a positive correlation was found between the gingival index and bleeding index versus the IL-1β levels in the pigmented healthy group. The pigmented gingivitis groups showed a negative correlation between the plaque index, gingival index and bleeding index. Conclusions: The clinical markers of inflammation such as gingival index, bleeding index was of low numerical value in pigmented group than in the non-pigmented group, supposedly due to the protective action of melanin. The negative correlation of clinical markers of inflammation to the IL-1β levels in the pigmented gingivitis group could possibly be attributed to the protective role of melanins.

  2. Adjusting total body iron for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

    Science.gov (United States)

    Mei, Zuguo; Namaste, Sorrel Ml; Serdula, Mary; Suchdev, Parminder S; Rohner, Fabian; Flores-Ayala, Rafael; Addo, O Yaw; Raiten, Daniel J

    2017-07-01

    Background: Total body iron (TBI) that is calculated from ferritin and soluble transferrin receptor (sTfR) allows for the evaluation of the full range of iron status from deficiency to excess. However, both ferritin and sTfR are affected by inflammation and malaria, which may require a statistical adjustment. TBI has been used to assess iron status in the United States, but its use worldwide and in settings with inflammation has been limited.Objective: We examine whether inflammation-adjusted ferritin and sTfR concentrations affect TBI values and the prevalence of low TBI (5 mg/L or α-1-acid glycoprotein concentration >1 g/L), 2) the application of arithmetic correction factors, and 3) the use of regression correction.Results: Regardless of the method that was used to adjust ferritin and sTfR for inflammation, the adjusted mean TBI decreased in both PSC and WRA compared with unadjusted values. Subsequently, inflammation-adjusted TBI increased the prevalence of low TBI by a median of 4-14 percentage points (pps) in PSC and 1-3 pps in WRA compared with unadjusted TBI. The regression approach resulted in a greater median increase than was achieved with the exclusion or correction-factor approaches, and accounting for malaria in addition to inflammation did not have an added effect on the prevalence estimates.Conclusion: The prevalence of low TBI is underestimated if it is not adjusted by inflammation, particularly in children living in areas with a high prevalence of inflammation.

  3. Treatment of orbital inflammation with rituximab in Wegener's granulomatosis

    DEFF Research Database (Denmark)

    Baslund, Bo; Wiencke, Anne Katrine; Rasmussen, Niels

    2012-01-01

    To study the efficacy of rituximab therapy for the treatment of orbital inflammation in patients with Wegener's granulomatosis (WG).......To study the efficacy of rituximab therapy for the treatment of orbital inflammation in patients with Wegener's granulomatosis (WG)....

  4. DMPD: Regulatory pathways in inflammation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17967718 Regulatory pathways in inflammation. Mantovani A, Garlanda C, Locati M, Ro....html) (.csml) Show Regulatory pathways in inflammation. PubmedID 17967718 Title Regulatory pathways in inflamma

  5. Adiponectin, biomarkers of inflammation and changes in cardiac autonomic function

    DEFF Research Database (Denmark)

    Hansen, Christian Stevns; Vistisen, Dorte; Jørgensen, Marit Eika

    2017-01-01

    BACKGROUND: Biomarkers of inflammation and adiponectin are associated with cardiovascular autonomic neuropathy (CAN) in cross-sectional studies, but prospective data are scarce. This study aimed to assess the associations of biomarkers of subclinical inflammation and adiponectin with subsequent...

  6. Drug Beats Steroids for Controlling Blood Vessel Inflammation in Study

    Science.gov (United States)

    ... html Drug Beats Steroids for Controlling Blood Vessel Inflammation in Study With tocilizumab's approval, there's an alternative ... treating the most common form of blood vessel inflammation known as giant cell arteritis, a new study ...

  7. Airway inflammation and mannitol challenge test in COPD

    NARCIS (Netherlands)

    de Nijs, Selma B.; Fens, Niki; Lutter, Rene; Dijkers, Erica; Krouwels, Frans H.; Smids-Dierdorp, Barbara S.; van Steenwijk, Reindert P.; Sterk, Peter J.

    2011-01-01

    ABSTRACT: BACKGROUND: Eosinophilic airway inflammation has successfully been used to tailor anti-inflammatory therapy in chronic obstructive pulmonary disease (COPD). Airway hyperresponsiveness (AHR) by indirect challenges is associated with airway inflammation. We hypothesized that AHR to inhaled

  8. Obesity and cancer: inflammation bridges the two.

    Science.gov (United States)

    Kolb, Ryan; Sutterwala, Fayyaz S; Zhang, Weizhou

    2016-08-01

    Obesity is a growing public health problem and affects 35% US adults. Obesity increases the risk of many cancer types and is associated with poor outcomes. Clinical management of cancer patients has been essentially the same between normal weight and obese individuals. Understanding causal mechanisms by which obesity drives cancer initiation and progression is essential for the development of novel precision therapy for obese cancer patients. One caveat is that various mechanisms have been proposed for different cancer types for their progression under obesity. Since obesity is known to have global impact on inflammation, here we will summarize recent literature and discuss the potential of inflammation being the common causal mechanism to promote cancer promotion across cancer types. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Inflammation Induces TDP-43 Mislocalization and Aggregation.

    Directory of Open Access Journals (Sweden)

    Ana Sofia Correia

    Full Text Available TAR DNA-binding protein 43 (TDP-43 is a major component in aggregates of ubiquitinated proteins in amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration (FTLD. Here we report that lipopolysaccharide (LPS-induced inflammation can promote TDP-43 mislocalization and aggregation. In culture, microglia and astrocytes exhibited TDP-43 mislocalization after exposure to LPS. Likewise, treatment of the motoneuron-like NSC-34 cells with TNF-alpha (TNF-α increased the cytoplasmic levels of TDP-43. In addition, the chronic intraperitoneal injection of LPS at a dose of 1mg/kg in TDP-43(A315T transgenic mice exacerbated the pathological TDP-43 accumulation in the cytoplasm of spinal motor neurons and it enhanced the levels of TDP-43 aggregation. These results suggest that inflammation may contribute to development or exacerbation of TDP-43 proteinopathies in neurodegenerative disorders.

  10. Adipocyte Death and Chronic Inflammation in Obesity.

    Science.gov (United States)

    Kuroda, Masashi; Sakaue, Hiroshi

    2017-01-01

    Cell death is closely linked to many diseases including cancer, neurodegenerative diseases, autoimmune diseases, and metabolic disorders. Increased adipocyte death has been reported during the development of obesity. Adipocyte death may be caused by excessive stress during obesity-related adipose tissue remodeling. Adipose tissue macrophages are key players in obesity-related inflammation and systemic insulin resistance. Accumulating evidence suggests that adipocyte death is involved in immune cell function and initiates inflammation through an interaction with macrophages; however, the precise mechanisms remain largely unknown. This review focuses on the contribution of dead cells (particularly dead adipocytes in adipose tissue) to the pathophysiological conditions associated with obesity. J. Med. Invest. 64: 193-196, August, 2017.

  11. Obesity and cancer: inflammation bridges the two

    Science.gov (United States)

    Kolb, Ryan; Sutterwala, Fayyaz S.; Zhang, Weizhou

    2016-01-01

    Obesity is a growing public health problem and affects 35% US adults. Obesity increases the risk of many cancer types and is associated with poor outcomes. Clinical management of cancer patients has been essentially the same between normal weight and obese individuals. Understanding causal mechanisms by which obesity drives cancer initiation and progression is essential for the development of novel precision therapy for obese cancer patients. One caveat is that various mechanisms have been proposed for different cancer types for their progression under obesity. Since obesity is known to have global impact on inflammation, here we will summarize recent literature and discuss the potential of inflammation being the common causal mechanism to promote cancer promotion across cancer types. PMID:27429211

  12. Chemical optogenetic modulation of inflammation and immunity.

    Science.gov (United States)

    Parasar, Bibudha; Chang, Pamela V

    2017-02-01

    The immune system is an essential component of host defense against pathogens and is largely mediated by inflammatory molecules produced by immune cells, such as macrophages. These inflammatory mediators are regulated at the transcriptional level by chromatin-modifying enzymes including histone deacetylases (HDACs). Here we describe a strategy to regulate inflammation and immunity with photocontrolled HDAC inhibitors, which can be selectively delivered to target cells by UV irradiation to minimize off-target effects. We strategically photocaged the active moiety of an HDAC inhibitor and showed that mild UV irradiation leads to the selective release of the inhibitor in a spatiotemporal manner. This methodology was used to decrease the amount of pro-inflammatory mediators produced by a subpopulation of macrophages. Our approach could ultimately be used to control inflammation in vivo as a therapeutic for inflammatory diseases, while minimizing off-target effects to healthy tissues.

  13. Delayed inflammation associated with retained perfluorocarbon liquid

    Directory of Open Access Journals (Sweden)

    S Pradeep

    2011-01-01

    Full Text Available A 55-year-old woman, with history of cataract surgery 1 year back, presented with features of ocular inflammation for last 3 months. She had no history of any other intraocular surgery. On examination, anterior segment showed frothy material in the inferior angle with moderate anterior chamber reaction (cells+/flare+ and sulcus intraocular lens with large posterior capsule rent. Fundoscopy showed multiple, small to medium-sized transparent bubbles of perfluorocarbon liquid (PFCL with membranes in the vitreous cavity. Ultrasonography confirmed the presence of PFCL in the vitreous cavity. Pars plana vitrectomy with anterior chamber wash was done which led to good visual recovery. To conclude, retained PFCL can cause late onset fibrinous inflammation after a quiescent period but surgical intervention may lead to good visual outcome.

  14. Matrix Metalloproteinases as Regulators of Periodontal Inflammation

    Science.gov (United States)

    Franco, Cavalla; Patricia, Hernández-Ríos; Timo, Sorsa; Claudia, Biguetti; Marcela, Hernández

    2017-01-01

    Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the ‘protease web’ is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing. Evidence points out that MMPs assemble in activation cascades and besides their classical extracellular matrix substrates, they cleave several signalling molecules—such as cytokines, chemokines, and growth factors, among others—regulating their biological functions and/or bioavailability during periodontal diseases. In this review, we provide an overview of emerging evidence of MMPs as regulators of periodontal inflammation. PMID:28218665

  15. Targeting inflammation in diabetes: Newer therapeutic options

    Science.gov (United States)

    Agrawal, Neeraj Kumar; Kant, Saket

    2014-01-01

    Inflammation has been recognised to both decrease beta cell insulin secretion and increase insulin resistance. Circulating cytokines can affect beta cell function directly leading to secretory dysfunction and increased apoptosis. These cytokines can also indirectly affect beta cell function by increasing adipocyte inflammation.The resulting glucotoxicity and lipotoxicity further enhance the inflammatory process resulting in a vicious cycle. Weight reduction and drugs such as metformin have been shown to decrease the levels of C-Reactive Protein by 31% and 13%, respectively. Pioglitazone, insulin and statins have anti-inflammatory effects. Interleukin 1 and tumor necrosis factor-α antagonists are in trials and NSAIDs such as salsalate have shown an improvement in insulin sensitivity. Inhibition of 12-lipo-oxygenase, histone de-acetylases, and activation of sirtuin-1 are upcoming molecular targets to reduce inflammation. These therapies have also been shown to decrease the conversion of pre-diabetes state to diabetes. Drugs like glicazide, troglitazone, N-acetylcysteine and selective COX-2 inhibitors have shown benefit in diabetic neuropathy by decreasing inflammatory markers. Retinopathy drugs are used to target vascular endothelial growth factor, angiopoietin-2, various proteinases and chemokines. Drugs targeting the proteinases and various chemokines are pentoxifylline, inhibitors of nuclear factor-kappa B and mammalian target of rapamycin and are in clinical trials for diabetic nephropathy. Commonly used drugs such as insulin, metformin, peroxisome proliferator-activated receptors, glucagon like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors also decrease inflammation. Anti-inflammatory therapies represent a potential approach for the therapy of diabetes and its complications. PMID:25317247

  16. Sarcopenia correlates with systemic inflammation in COPD.

    Science.gov (United States)

    Byun, Min Kwang; Cho, Eun Na; Chang, Joon; Ahn, Chul Min; Kim, Hyung Jung

    2017-01-01

    Muscle wasting and chronic inflammation are predominant features of patients with COPD. Systemic inflammation is associated with an accelerated decline in lung function. In this study, the prevalence of sarcopenia and the relationships between sarcopenia and systemic inflammations in patients with stable COPD were investigated. In a cross-sectional design, muscle strength and muscle mass were measured by handgrip strength (HGS) and bioelectrical impedance analysis in 80 patients with stable COPD. Patients (≥40 years old) diagnosed with COPD were recruited from outpatient clinics, and then COPD stages were classified. Sarcopenia was defined as the presence of both low muscle strength (by HGS) and low muscle mass (skeletal muscle mass index [SMMI]). Levels of circulating inflammatory biomarkers (IL-6 and high-sensitivity TNFα [hsTNFα]) were measured. Sarcopenia was prevalent in 20 (25%) patients. Patients with sarcopenia were older, had lower body mass index, and a higher percentage of cardiovascular diseases. In addition, they had significantly higher modified Medical Research Council scores and lower 6-minute walk distance than those without sarcopenia. HGS was significantly correlated with age, modified Medical Research Council score, and COPD Assessment Test scores. Both HGS and SMMI had associations with IL-6 and hsTNFα (HGS, r =-0.35, P =0.002; SMMI, r =-0.246, P =0.044) level. In multivariate analysis, old age, lower body mass index, presence of cardiovascular comorbidities, and higher hsTNFα levels were significant determinants for sarcopenia in patients with stable COPD. Sarcopenia is very common in patients with stable COPD, and is associated with more severe dyspnea-scale scores and lower exercise tolerance. Systemic inflammation could be an important contributor to sarcopenia in the stable COPD population.

  17. Sirtuin 2 Regulates Microvascular Inflammation during Sepsis

    Directory of Open Access Journals (Sweden)

    Nancy Buechler

    2017-01-01

    Full Text Available Objective. Sepsis and septic shock, the leading causes of death in noncoronary intensive care units, kill more than 200,000/year in the US alone. Circulating cell-endothelial cell interactions are the rate determining factor in sepsis inflammation. Sirtuin, a seven-member family of proteins (SIRT1–7, epigenetically controls inflammation. We have studied the roles of SIRTs 1, 3, and 6 in sepsis previously. In this project, we studied the role of SIRT2 on sepsis-related inflammation. Methods. Sepsis was induced in C57Bl/6 (WT, SIRT2 knockout (SIRT2KO, and SIRT2 overexpressing (SIRT2KI mice by cecal ligation and puncture (CLP. We studied leukocyte/platelet adhesion using intravital microscopy and E-selectin/ICAM-1 adhesion molecule expression in the small intestine with immunohistochemistry (IHC six hours post-CLP/sham surgery. We also studied 7-day survival rates in WT, SIRT2KO, and SIRT2KI sepsis mice. Results. Compared to WT mice, SIRT2KO mice show exaggeration while SIRT2KI mice show attenuation of cellular adhesion with sepsis in the small intestine. We also show that the small intestinal E-selectin and ICAM-1 expressions increased in SIRT2KO and decreased in SIRT2KI mice versus those in WT sepsis mice. We show that the 7-day survival rate is decreased in SIRT2KO and increased in SIRT2KI sepsis mice. Conclusion. SIRT2 modulates microvascular inflammation in sepsis and affects survival.

  18. Rab GTPases in Immunity and Inflammation

    Science.gov (United States)

    Prashar, Akriti; Schnettger, Laura; Bernard, Elliott M.; Gutierrez, Maximiliano G.

    2017-01-01

    Strict spatiotemporal control of trafficking events between organelles is critical for maintaining homeostasis and directing cellular responses. This regulation is particularly important in immune cells for mounting specialized immune defenses. By controlling the formation, transport and fusion of intracellular organelles, Rab GTPases serve as master regulators of membrane trafficking. In this review, we discuss the cellular and molecular mechanisms by which Rab GTPases regulate immunity and inflammation. PMID:29034219

  19. Rab GTPases in Immunity and Inflammation

    Directory of Open Access Journals (Sweden)

    Akriti Prashar

    2017-09-01

    Full Text Available Strict spatiotemporal control of trafficking events between organelles is critical for maintaining homeostasis and directing cellular responses. This regulation is particularly important in immune cells for mounting specialized immune defenses. By controlling the formation, transport and fusion of intracellular organelles, Rab GTPases serve as master regulators of membrane trafficking. In this review, we discuss the cellular and molecular mechanisms by which Rab GTPases regulate immunity and inflammation.

  20. Role of inflammation in nocturnal asthma.

    OpenAIRE

    MacKay, T. W.; Wallace, W A; Howie, S. E.; Brown, P. H.; Greening, A P; Church, M. K.; Douglas, N. J.

    1994-01-01

    BACKGROUND--Nocturnal airway narrowing is a common problem for patients with asthma but the role of inflammation in its pathogenesis is unclear. Overnight changes in airway inflammatory cell populations were studied in patients with nocturnal asthma and in control normal subjects. METHODS--Bronchoscopies were performed at 0400 hours and 1600 hours in eight healthy subjects and in 10 patients with nocturnal asthma (> 15% overnight fall in peak flow plus at least one awakening/week with asthma)...

  1. Molecular MRI of neurovascular inflammation and angiogenesis

    OpenAIRE

    Deddens, L.H.

    2013-01-01

    This thesis describes the use of different MR contrast agent platforms for the direct detection of pathology-induced upregulation of intraluminally-expressed vascular entities by molecular MRI. We particularly focused on the in vivo target specificity and MR sensitivity of the agents. The biological targets of our molecular MRI approaches were associated with two types of vascular events that are critically involved in many pathologies; i.e., angiogenesis and neurovascular inflammation. In Ch...

  2. Sphingolipid Metabolism and Obesity-Induced Inflammation

    OpenAIRE

    Se-Chan eKang; Bo-Rahm eKim; Su-Yeon eLee; Tae-Sik ePark

    2013-01-01

    Obesity is a metabolic disorder developed by overnutrition and a major cause for insulin resistance and cardiovascular events. Since adipose tissue is one of the major sites for the synthesis and secretion of cytokines, enlarged adipose tissue in obese condition alters inflammatory state leading to pathophysiological conditions such as type 2 diabetes and increased cardiovascular risk. A plausible theory for development of metabolic dysregulation is that obesity increases secretion of inflamm...

  3. Two faces of inflammation: an immunopharmacological view.

    Science.gov (United States)

    Moilanen, Eeva

    2014-01-01

    Inflammation is a protective response intended to eliminate pathogens and other offending agents which have potential to cause cell injury, as well as malignant and necrotic cells. However, if the inflammatory response is dysregulated or inappropriately focused, it has considerable potential to cause harm and can lead to development of inflammatory diseases such as allergic and autoimmune diseases. Despite the recent success in cytokine-targeted therapies, for example by the use of specific biological drugs, there are still considerable unmet needs in the treatment of inflammatory diseases. Further, recent discoveries in many diseases in addition to the classical inflammatory diseases have revealed inflammation to be a major factor participating in the underlying pathophysiological processes, either through activation of inflammatory cells or through triggering of inflammatory signalling mechanisms in the tissue cells. Examples of such diseases and conditions are many cardiovascular, metabolic and degenerative diseases, as well as cancer, obesity and pain. This brings the immunopharmacological approach into a new perspective in the drug development in very wide therapeutic areas. Immunopharmacology investigates mechanisms of inflammation and potential molecules and targets to treat inflammatory diseases. The current issue of Basic and Clinical Pharmacology and Toxicology focuses on some of the novel inflammatory mechanisms with potential in anti-inflammatory drug development, including kinase pathways, TRP ion channels, eicosanoid system, obesity-related adipokines, autoantibodies against citrullinated proteins, eosinophils, platelets and pathways connecting nervous and immune systems. The MiniReviews are based on lectures given at the symposium "Novel Drugs and Drug Targets to Treat Inflammation" in Ylläs, Finland, in March 2013. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

  4. Inflammation - Cause or Consequence of Heart Failure or Both?

    Science.gov (United States)

    Van Linthout, Sophie; Tschöpe, Carsten

    2017-08-01

    With the intention to summarize the currently available evidence on the pathophysiological relevance of inflammation in heart failure, this review addresses the question whether inflammation is a cause or consequence of heart failure, or both. This review discusses the diversity (sterile, para-inflammation, chronic inflammation) and sources of inflammation and gives an overview of how inflammation (local versus systemic) can trigger heart failure. On the other hand, the review is outlined how heart failure-associated wall stress and signals released by stressed, malfunctioning, or dead cells (DAMPs: e.g., mitochondrial DNA, ATP, S100A8, matricellular proteins) induce cardiac sterile inflammation and how heart failure provokes inflammation in various peripheral tissues in a direct (inflammatory) and indirect (hemodynamic) manner. The crosstalk between the heart and peripheral organs (bone marrow, spleen, gut, adipose tissue) is outlined and the importance of neurohormonal mechanisms including the renin angiotensin aldosteron system and the ß-adrenergic nervous system in inflammation and heart failure is discussed. Inflammation and heart failure are strongly interconnected and mutually reinforce each other. This indicates the difficulty to counteract inflammation and heart failure once this chronic vicious circle has started and points out the need to control the inflammatory process at an early stage avoiding chronic inflammation and heart failure. The diversity of inflammation further addresses the need for a tailored characterization of inflammation enabling differentiation of inflammation and subsequent target-specific strategies. It is expected that the characterization of the systemic and/or cardiac immune profile will be part of precision medicine in the future of cardiology.

  5. The Enteric Nervous System in Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Keith A Sharkey

    1996-01-01

    Full Text Available Since about the 1950s nerves in the wall of the intestine have been postulated to play a role in the pathogenesis of inflammatory bowel disease (IBD. Human and animal studies examining the role of nerves in intestinal inflammation are the focus of this review. Consideration is given to two possible ways that nerves are involved in IBD. First, nerves may play a role in the development or maintenance of inflammation through local release of transmitters. Second, once initiated (by whatever means, the processes of inflammation may disrupt the normal pattern of innervation and the interactions of nerves and their target tissues. Many of the functional disturbances observed in IBD are likely due to an alteration in the enteric nervous system either structurally through disruptions of nerve-target relationships or by modifications of neurotransmitters or their receptors. Finally, it appears that the enteric nervous system may be a potential therapeutic target in IBD and that neuroactive drugs acting locally can represent useful agents in the management of this disease.

  6. Dysbiosis in intestinal inflammation: Cause or consequence.

    Science.gov (United States)

    Buttó, Ludovica F; Haller, Dirk

    2016-08-01

    The intestinal microbiota encompasses hundreds of bacterial species that constitute a relatively stable ecosystem. Alteration in the microbiota composition may arise from infections, immune defects, metabolic alterations, diet or antibiotic treatment. Dysbiosis is considered as an alteration in microbiota community structure and/or function, capable of causing/driving a detrimental distortion of microbe-host homeostasis. A variety of pathologies are associated with changes in the community structure and function of the gut microbiota, suggesting a link between dysbiosis and disease etiology. With an emphasis in this review on inflammatory bowel diseases (IBD), the non-trivial question is whether dysbiosis is the cause or consequence of inflammation. It is important to understand whether changes in microbial ecosystems are causally linked to the pathology and to what extend disease risk is predicable based on characteristic changes in community structure and/or function. Local changes in tissue integrity associated with focal areas of inflammation may result in the selection of a dysbiotic bacterial community associated with the propagation of a disease phenotype. This review outlines the role of dysbiosis in intestinal inflammation with particular focus on IBD-relevant gnotobiotic mouse models, the factors implicated in the development of dysbiosis and the means available to investigate dysbiosis in the context of human diseases. Copyright © 2016 Elsevier GmbH. All rights reserved.

  7. Implants and inflammation - Where is the future?

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    Karim El Kholy

    2015-01-01

    Full Text Available The demand for dental implants continues to increase. Implants have replaced fixed and removable prosthetics as the gold standard for replacing missing teeth. Despite the success of the majority of dental implants, biological complications in the form of peri-implant inflammation are common and present as a challenge for both patients and clinicians. The pathogenesis of peri-implantitis was found to be similar to periodontitis. Both are initiated by a bacterial biofilm composed of similar micro-organisms. The inflammatory reaction to the established biofilm is responsible for disease progression and most of the resultant tissue destruction. Treatment strategies for peri-implantitis have mainly been focused on the removal of the bacterial etiology. Limited access and implant surface roughness have proven to be tough challenges for decontaminating exposed implant surfaces. The few attempts using host modulating agents have been abandoned due to drug-associated side effects. Recently, new signaling pathways and molecules involved in the natural resolution of inflammation have been discovered. These indigenous proresolving lipid mediator receptor agonists, such as lipoxins, resolvins, and protectins, provide an opportunity to regulate inflammation in chronic inflammatory diseases such as peri-implantitis while avoiding the undesirable side effects of inhibitory pharmacological agents.

  8. Congenital muscular dystrophy with inflammation: Diagnostic considerations

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    Kaumudi Konkay

    2016-01-01

    Full Text Available Background and Purpose: Muscle biopsy features of congenital muscular dystrophies (CMD vary from usual dystrophic picture to normal or nonspecific myopathic picture or prominent fibrosis or striking inflammatory infiltrate, which may lead to diagnostic errors. A series of patients of CMD with significant inflammatory infiltrates on muscle biopsy were correlated with laminin α 2 deficiency on immunohistochemistry (IHC. Material and Methods: Cryostat sections of muscle biopsies from the patients diagnosed as CMD on clinical and muscle biopsy features from 1996 to 2014 were reviewed with hematoxylin and eosin(H&E, enzyme and immunohistochemistry (IHC with laminin α 2. Muscle biopsies with inflammatory infiltrate were correlated with laminin α 2 deficiency. Results: There were 65 patients of CMD, with inflammation on muscle biopsy in 16. IHC with laminin α 2 was available in nine patients, of which six showed complete absence along sarcolemma (five presented with floppy infant syndrome and one with delayed motor milestones and three showed discontinuous, and less intense staining. Conclusions: CMD show variable degrees of inflammation on muscle biopsy. A diagnosis of laminin α 2 deficient CMD should be considered in patients of muscular dystrophy with inflammation, in children with hypotonia/delayed motor milestones.

  9. PAIN AND INFLAMMATION. PART 1. PATHOGENETIC ASPECTS

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    A. E. Karateev

    2016-01-01

    Full Text Available The relief of suffering, which is associated with a rapid and complete elimination of painful sensations, is the most important challenge facing physicians of many specialties. It is obvious that it can be solved only when you understand clearly the processes governing the development and chronization of pain. Inflammation, a universal adaptive mechanism that always accompanies damage to living tissues, plays a key role. Part 1 of this review considers the main stages of development of an inflammatory response, beginning with primary damage accompanied by the release of molecules acting as an alarm and ending with the deployment of a complete picture of the inflammatory response with the involvement of many cell elements and the overexpression of cytokines and proinflammatory mediators. The biological basis of the peripheral and central nociceptive sensitization phenomenon that is rigidly associated with inflammation is presented. Particular emphasis is placed on the possible natural completion of the inflammatory response, on the adaptive mechanisms regulating this process and on the reasons that prevent this and determines inflammation chronization.

  10. Salivary cytokine levels in early gingival inflammation

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Damgaard, Christian; Könönen, Eija

    2017-01-01

    Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte chemoattr......Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte...... chemoattractant protein (MCP)-1, IL-1β, and IL-1 receptor antagonist (IL-1Ra) in gingival inflammation. Twenty-eight systemically and orally healthy nonsmokers abstained from oral hygiene protocols for 10 days. After that, self-performed cleaning was resumed for 14 days. Plaque and gingival indexes were measured......, and saliva samples were collected at days 1, 4, 7, 10, and 24. Salivary cytokines were detected with Luminex®-xMAP™. Salivary IL-1β, IL-1Ra, and VEGF levels decreased after 10 days' development of experimental gingivitis and reached baseline levels at the end of the 2-week resolution period. Salivary IL-8...

  11. Neurobehavioral comorbidities of epilepsy: Role of inflammation.

    Science.gov (United States)

    Mazarati, Andrey M; Lewis, Megan L; Pittman, Quentin J

    2017-07-01

    Epilepsy is associated with a high incidence of comorbid neurologic and psychiatric disorders. This review focuses on the association of epilepsy with autism spectrum disorder (ASD) and depression. There is high concordance of these behavioral pathologies with epilepsy. We review data that unambiguously reveal that epilepsy, ASD, and depression are associated with elevated brain inflammatory markers and that these may interact with serotoninergic pathways. Interference with inflammatory pathways or actions can reduce the severity of seizures, depression, and ASD-like behavior. Inflammation in the brain can be induced by seizure activity as well as by behavioral, environmental, and physiologic stressors. Furthermore, induction of inflammation at an early time point during gestation and in early neonatal life can precipitate both an ASD-like phenotype as well as a more excitable brain. It appears likely that priming of the brain due to early inflammation could provide a means by which subsequent inflammatory processes associated with epilepsy, ASD, and depression may lead to comorbidity. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  12. Ageing, adipose tissue, fatty acids and inflammation.

    Science.gov (United States)

    Pararasa, Chathyan; Bailey, Clifford J; Griffiths, Helen R

    2015-04-01

    A common feature of ageing is the alteration in tissue distribution and composition, with a shift in fat away from lower body and subcutaneous depots to visceral and ectopic sites. Redistribution of adipose tissue towards an ectopic site can have dramatic effects on metabolic function. In skeletal muscle, increased ectopic adiposity is linked to insulin resistance through lipid mediators such as ceramide or DAG, inhibiting the insulin receptor signalling pathway. Additionally, the risk of developing cardiovascular disease is increased with elevated visceral adipose distribution. In ageing, adipose tissue becomes dysfunctional, with the pathway of differentiation of preadipocytes to mature adipocytes becoming impaired; this results in dysfunctional adipocytes less able to store fat and subsequent fat redistribution to ectopic sites. Low grade systemic inflammation is commonly observed in ageing, and may drive the adipose tissue dysfunction, as proinflammatory cytokines are capable of inhibiting adipocyte differentiation. Beyond increased ectopic adiposity, the effect of impaired adipose tissue function is an elevation in systemic free fatty acids (FFA), a common feature of many metabolic disorders. Saturated fatty acids can be regarded as the most detrimental of FFA, being capable of inducing insulin resistance and inflammation through lipid mediators such as ceramide, which can increase risk of developing atherosclerosis. Elevated FFA, in particular saturated fatty acids, maybe a driving factor for both the increased insulin resistance, cardiovascular disease risk and inflammation in older adults.

  13. Silibinin attenuates allergic airway inflammation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yun Ho [Department of Anatomy, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Jin, Guang Yu [Department of Radiology, Yanbian University Hospital, YanJi 133002 (China); Guo, Hui Shu [Centralab, The First Affiliated Hospital of Dalian Medical University, Dalian 116011 (China); Piao, Hong Mei [Department of Respiratory Medicine, Yanbian University Hospital, YanJi 133000 (China); Li, Liang chang; Li, Guang Zhao [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China); Lin, Zhen Hua [Department of Pathology, Yanbian University School of Basic Medical Sciences, YanJi 133000 (China); Yan, Guang Hai, E-mail: ghyan@ybu.edu.cn [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  14. The resolution of inflammation: Principles and challenges.

    Science.gov (United States)

    Headland, Sarah E; Norling, Lucy V

    2015-05-01

    The concept that chemokines, cytokines and pro-inflammatory mediators act in a co-ordinated fashion to drive the initiation of the inflammatory reaction is well understood. The significance of such networks acting during the resolution of inflammation however is poorly appreciated. In recent years, specific pro-resolving mediators were discovered which activate resolution pathways to return tissues to homeostasis. These mediators are diverse in nature, and include specialized lipid mediators (lipoxins, resolvins, protectins and maresins) proteins (annexin A1, galectins) and peptides, gaseous mediators including hydrogen sulphide, a purine (adenosine), as well as neuromodulator release under the control of the vagus nerve. Functionally, they can act to limit further leukocyte recruitment, induce neutrophil apoptosis and enhance efferocytosis by macrophages. They can also switch macrophages from classical to alternatively activated cells, promote the return of non-apoptotic cells to the lymphatics and help initiate tissue repair mechanisms and healing. Within this review we highlight the essential cellular aspects required for successful tissue resolution, briefly discuss the pro-resolution mediators that drive these processes and consider potential challenges faced by researchers in the quest to discover how inflammation resolves and why chronic inflammation persists. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Dietary fiber, inflammation, and cardiovascular disease.

    Science.gov (United States)

    King, Dana E

    2005-06-01

    The role of dietary fiber in the prevention of cardiovascular disease has received increasing attention as data have accumulated. Recent cohort studies have found a consistent protective effect of dietary fiber on cardiovascular disease outcomes, prompting many leading organizations to recommend increased fiber in the daily diet. However, the biologic mechanisms explaining how a fiber influences the cardiovascular system have yet to be fully elucidated. Recent research in large national sample in the USA has demonstrated an association between dietary fiber and levels of C-reactive protein (CRP), a clinical indicator of inflammation. Epidemiologic evidence demonstrating that high-fiber diets are beneficial, coupled with this newer evidence of a possible metabolic effect on inflammatory markers, suggest that inflammation may be an important mediator in the association between dietary fiber and cardiovascular disease (CVD). This paper reviews the evidence for the connections among inflammation, CRP, dietary fiber, and CVD, and recommends further clinical studies using fiber supplementation to isolate and prospectively confirm these important relationships.

  16. Interleukin-33 modulates inflammation in endometriosis.

    Science.gov (United States)

    Miller, Jessica E; Monsanto, Stephany P; Ahn, Soo Hyun; Khalaj, Kasra; Fazleabas, Asgerally T; Young, Steven L; Lessey, Bruce A; Koti, Madhuri; Tayade, Chandrakant

    2017-12-20

    Endometriosis is a debilitating condition that is categorized by the abnormal growth of endometrial tissue outside the uterus. Although the pathogenesis of this disease remains unknown, it is well established that endometriosis patients exhibit immune dysfunction. Interleukin (IL)-33 is a danger signal that is a critical regulator of chronic inflammation. Although plasma and peritoneal fluid levels of IL-33 have been associated with deep infiltrating endometriosis, its contribution to the disease pathophysiology is unknown. We investigated the role of IL-33 in the pathology of endometriosis using patient samples, cell lines and a syngeneic mouse model. We found that endometriotic lesions produce significantly higher levels of IL-33 compared to the endometrium of healthy, fertile controls. In vitro stimulation of endometrial epithelial, endothelial and endometriotic epithelial cells with IL-33 led to the production of pro-inflammatory and angiogenic cytokines. In a syngeneic mouse model of endometriosis, IL-33 injections caused systemic inflammation, which manifested as an increase in plasma pro-inflammatory cytokines compared to control mice. Furthermore, endometriotic lesions from IL-33 treated mice were highly vascularized and exhibited increased proliferation. Collectively, we provide convincing evidence that IL-33 perpetuates inflammation, angiogenesis and lesion proliferation, which are critical events in the lesion survival and progression of endometriosis.

  17. Stress, and Inflammation in Young Soccer Players

    Directory of Open Access Journals (Sweden)

    Ivana Baralic

    2015-01-01

    Full Text Available The physiologic stress induced by physical activity is reflected in immune system perturbations, oxidative stress, muscle injury, and inflammation. We investigated the effect of astaxanthin (Asx supplementation on salivary IgA (sIgA and oxidative stress status in plasma, along with changes in biochemical parameters and total/differential white cell counts. Forty trained male soccer players were randomly assigned to Asx and placebo groups. Asx group was supplemented with 4 mg of Asx. Saliva and blood samples were collected at the baseline and after 90 days of supplementation in preexercise conditions. We observed a rise of sIgA levels at rest after 90 days of Asx supplementation, which was accompanied with a decrease in prooxidant-antioxidant balance. The plasma muscle enzymes levels were reduced significantly by Asx supplementation and by regular training. The increase in neutrophil count and hs-CRP level was found only in placebo group, indicating a significant blunting of the systemic inflammatory response in the subjects taking Asx. This study indicates that Asx supplementation improves sIgA response and attenuates muscle damage, thus preventing inflammation induced by rigorous physical training. Our findings also point that Asx could show significant physiologic modulation in individuals with mucosal immunity impairment or under conditions of increased oxidative stress and inflammation.

  18. Probiotics as regulators of inflammation: A review

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    David W. Lescheid

    2014-07-01

    Full Text Available A substantial and increasing body of clinical evidence supports the role of specific strains and mixtures of probiotics in the prevention and treatment of certain diseases. Several general mechanisms of action have been proposed, including supporting repair of hyperpermeable epithelial barriers, interfering with infection by pathogens, and restoring a healthful balance of commensal microbes to affect metabolism. Emerging evidence supports an additional role of probiotics as important modulators of immune system responses, including inflammation, at mucosal surfaces. In particular, by preventing or repairing ‘leaky’ epithelial barriers, probiotics can indirectly affect the inflammatory response by negating the source of pro-inflammatory stimuli associated with low-grade endotoxemia. They also enhance production of short chain fatty acids with anti-inflammatory properties (e.g. butyrate as well as increase synthesis of antimicrobial peptides that influence inflammation resolution pathways in the mucosa. Furthermore, probiotics and some of their secreted metabolic products can act as ligands for innate immune system receptors, directly influencing key pro-inflammatory pathways. They also stimulate the differentiation and activity of important immune cells (e.g., dendritic cells, T cells, and subsequently increase production of important regulatory cytokines, including interleukin-10 (IL-10 and transforming growth factor-beta (TGF-. Finally, there are limited but increasing animal studies and clinical trials demonstrating probiotics do affect common biomarkers of inflammation, including C-reactive protein, as well as signs and symptoms of the associated diseases suggesting they can have therapeutic benefit in the treatment of chronic inflammatory disease

  19. Oxidative stress and vascular inflammation in aging.

    Science.gov (United States)

    El Assar, Mariam; Angulo, Javier; Rodríguez-Mañas, Leocadio

    2013-12-01

    Vascular aging, a determinant factor for cardiovascular disease and health status in the elderly, is now viewed as a modifiable risk factor. Impaired endothelial vasodilation is a early hallmark of arterial aging that precedes the clinical manifestations of vascular dysfunction, the first step to cardiovascular disease and influencing vascular outcomes in the elderly. Accordingly, the preservation of endothelial function is thought to be an essential determinant of healthy aging. With special attention on the effects of aging on the endothelial function, this review is focused on the two main mechanisms of aging-related endothelial dysfunction: oxidative stress and inflammation. Aging vasculature generates an excess of the reactive oxygen species (ROS), superoxide and hydrogen peroxide, that compromise the vasodilatory activity of nitric oxide (NO) and facilitate the formation of the deleterious radical, peroxynitrite. Main sources of ROS are mitochondrial respiratory chain and NADPH oxidases, although NOS uncoupling could also account for ROS generation. In addition, reduced antioxidant response mediated by erythroid-2-related factor-2 (Nrf2) and downregulation of mitochondrial manganese superoxide dismutase (SOD2) contributes to the establishment of chronic oxidative stress in aged vessels. This is accompanied by a chronic low-grade inflammatory phenotype that participates in defective endothelial vasodilation. The redox-sensitive transcription factor, nuclear factor-κB (NF-κB), is upregulated in vascular cells from old subjects and drives a proinflammatory shift that feedbacks oxidative stress. This chronic NF-κB activation is contributed by increased angiotensin-II signaling and downregulated sirtuins and precludes adequate cellular response to acute ROS generation. Interventions targeted to recover endogenous antioxidant capacity and cellular stress response rather than exogenous antioxidants could reverse oxidative stress-inflammation vicious cycle in

  20. Suppression of Th17-polarized airway inflammation by rapamycin.

    Science.gov (United States)

    Joean, Oana; Hueber, Anja; Feller, Felix; Jirmo, Adan Chari; Lochner, Matthias; Dittrich, Anna-Maria; Albrecht, Melanie

    2017-11-10

    Because Th17-polarized airway inflammation correlates with poor control in bronchial asthma and is a feature of numerous other difficult-to-treat inflammatory lung diseases, new therapeutic approaches for this type of airway inflammation are necessary. We assessed different licensed anti-inflammatory agents with known or expected efficacy against Th17-polarization in mouse models of Th17-dependent airway inflammation. Upon intravenous transfer of in vitro derived Th17 cells and intranasal challenge with the corresponding antigen, we established acute and chronic murine models of Th17-polarised airway inflammation. Consecutively, we assessed the efficacy of methylprednisolone, roflumilast, azithromycin, AM80 and rapamycin against acute or chronic Th17-dependent airway inflammation. Quantifiers for Th17-associated inflammation comprised: bronchoalveolar lavage (BAL) differential cell counts, allergen-specific cytokine and immunoglobulin secretion, as well as flow cytometric phenotyping of pulmonary inflammatory cells. Only rapamycin proved effective against acute Th17-dependent airway inflammation, accompanied by increased plasmacytoid dendritic cells (pDCs) and reduced neutrophils as well as reduced CXCL-1 levels in BAL. Chronic Th17-dependent airway inflammation was unaltered by rapamycin treatment. None of the other agents showed efficacy in our models. Our results demonstrate that Th17-dependent airway inflammation is difficult to treat with known agents. However, we identify rapamycin as an agent with inhibitory potential against acute Th17-polarized airway inflammation.

  1. Magnesium deficiency and increased inflammation: current perspectives

    Directory of Open Access Journals (Sweden)

    Nielsen FH

    2018-01-01

    Full Text Available Forrest H Nielsen Research Nutritionist Consultant, Grand Forks, ND, USA Abstract: Animal studies have shown that magnesium deficiency induces an inflammatory response that results in leukocyte and macrophage activation, release of inflammatory cytokines and acute-phase proteins, and excessive production of free radicals. Animal and in vitro studies indicate that the primary mechanism through which magnesium deficiency has this effect is through increasing cellular Ca2+, which is the signal that results in the priming of cells to give the inflammatory response. Primary pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL-1; the messenger cytokine IL-6; cytokine responders E-selectin, intracellular adhesion molecule-1 and vascular cell adhesion molecule-1; and acute-phase reactants C-reactive protein and fibrinogen have been determined to associate magnesium deficiency with chronic low-grade inflammation (inflammatory stress. When magnesium dietary intake, supplementation, and/or serum concentration suggest/s the presence of magnesium deficiency, it often is associated with low-grade inflammation and/or with pathological conditions for which inflammatory stress is considered a risk factor. When magnesium intake, supplementation, and/or serum concentration suggest/s an adequate status, magnesium generally has not been found to significantly affect markers of chronic low-grade inflammation or chronic disease. The consistency of these findings can be modified by other nutritional and metabolic factors that affect inflammatory and oxidative stress. In spite of this, findings to date provide convincing evidence that magnesium deficiency is a significant contributor to chronic low-grade inflammation that is a risk factor for a variety of pathological conditions such as cardiovascular disease, hypertension, and diabetes. Because magnesium deficiency commonly occurs in countries where foods rich in magnesium are not consumed in

  2. Innate immune cells in inflammation and cancer.

    Science.gov (United States)

    Nowarski, Roni; Gagliani, Nicola; Huber, Samuel; Flavell, Richard A

    2013-08-01

    The innate immune system has evolved in multicellular organisms to detect and respond to situations that compromise tissue homeostasis. It comprises a set of tissue-resident and circulating leukocytes primarily designed to sense pathogens and tissue damage through hardwired receptors and eliminate noxious sources by mediating inflammatory processes. While indispensable to immunity, the inflammatory mediators produced in situ by activated innate cells during injury or infection are also associated with increased cancer risk and tumorigenesis. Here, we outline basic principles of innate immune cell functions in inflammation and discuss how these functions converge upon cancer development. ©2013 AACR.

  3. Persistent Inflammation, Immunosuppression and Catabolism Syndrome.

    Science.gov (United States)

    Mira, Juan C; Brakenridge, Scott C; Moldawer, Lyle L; Moore, Frederick A

    2017-04-01

    Following advances in critical care, in-hospital multiple organ failure-related mortality is declining. Consequently, incidence of chronic critical illness is increasing. These patients linger in the intensive care unit, have high resource utilization, and poor long-term outcomes. Within this population, the authors propose that a substantial subset of patients have a new phenotype: persistent inflammation, immunosuppression, and catabolism syndrome. There is evidence that myelodysplasia with expansion of myeloid-derived suppressor cells, innate and adaptive immune suppression, and protein catabolism with malnutrition are major contributors. Optimal care of these patients will require novel multimodality interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Vagus nerve modulation of inflammation: Cardiovascular implications.

    Science.gov (United States)

    Olshansky, Brian

    2016-01-01

    The vagus nerve modulates inflammatory responses in various organ systems. Emerging evidence indicates that the vagus can have profound and complex effects on cardiovascular function, remodeling, arrhythmias, and mortality by several mechanisms. In heart failure and during ischemia, an adverse inflammatory response can occur. The vagus nerve may modulate cardiovascular disease and outcomes by affecting inflammatory responses. Here, evidence for and components of the vagus inflammatory reflex are reviewed and evidence for and implications of effects of vagus activation on inflammation in the cardiovascular system are considered. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. STUDIES ON INFLAMMATION : VII. FIXATION OF BACTERIA AND OF PARTICULATE MATTER AT THE SITE OF INFLAMMATION.

    Science.gov (United States)

    Menkin, V

    1931-04-30

    India ink or graphite partides injected into an area of inflammation fail to disseminate to the tributary lymph nodes. When injected into a normal peritoneal cavity they rapidly appear in the retrosternal lymph nodes. When injected into an inflamed peritoneal cavity they are fixed in situ and fail to reach the regional lymph nodes. Graphite particles injected in the circulating blood stream enter an inflamed area both as free particles owing to increased capillary permeability and also as phagocyted material within leucocytes. Bacteria (B. prodigiosus) injected into inflamed tissue are fixed at the site of inflammation and fail to disseminate to the regional lymph nodes as readily as when injected into normal tissue. Bacteria (B. prodigiosus) injected at the periphery of an inflamed area do not readily penetrate into the site of inflammation. The experiments furnish evidence, in addition to that already provided, that fixation of foreign substances by the inflammatory reaction is primarily due to mechanical obstruction caused by a fibrin network and by thrombosed lymphatics at the site of inflammation. Bacteria (B. prodigiosus and B. pyocyaneus) injected intravenously rapidly enter an inflamed area. It is suggested that localization of bacteria in a locus minoris resistentiae may be explained as the result of increased capillary permeability with subsequent accumulation and fixation of bacteria from the blood stream at the point of injury.

  6. Adjusting ferritin concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

    Science.gov (United States)

    Namaste, Sorrel Ml; Rohner, Fabian; Huang, Jin; Bhushan, Nivedita L; Flores-Ayala, Rafael; Kupka, Roland; Mei, Zuguo; Rawat, Rahul; Williams, Anne M; Raiten, Daniel J; Northrop-Clewes, Christine A; Suchdev, Parminder S

    2017-07-01

    Background: The accurate estimation of iron deficiency is important in planning and implementing interventions. Ferritin is recommended as the primary measure of iron status, but interpretability is challenging in settings with infection and inflammation. Objective: We assessed the relation between ferritin concentrations and inflammation and malaria in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y) and investigated adjustment algorithms to account for these effects. Design: Cross-sectional data from 15 surveys for PSC ( n = 27,865) and 8 surveys for WRA (24,844), from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and combined with the use of a meta-analysis. Several approaches were explored to estimate depleted iron stores (ferritin concentration inflammation and malaria settings as follows: 1 ) increase ferritin-concentration cutoff to 5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L; 3 ) apply arithmetic correction factors; and 4 ) use a regression correction approach. Results: Depleted iron-store estimates incrementally increased as CRP and AGP deciles decreased (4% compared with 30%, and 6% compared with 29% from highest compared with lowest CRP deciles for pooled PSC and WRA, respectively, with similar results for AGP). Depending on the approach used to adjust for inflammation (CRP plus AGP), the estimated prevalence of depleted iron stores increased by 7-25 and 2-8 absolute median percentage points for PSC and WRA, respectively, compared with unadjusted values. Adjustment for malaria in addition to CRP and AGP did not substantially change the estimated prevalence of depleted iron stores. Conclusions: Our results lend support for the use of internal regression correction to estimate the prevalence of depleted iron stores in regions with inflammation. This approach appears to mathematically reflect the linear

  7. Adjusting ferritin concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

    Science.gov (United States)

    Huang, Jin; Bhushan, Nivedita L; Flores-Ayala, Rafael; Kupka, Roland; Mei, Zuguo; Rawat, Rahul; Williams, Anne M; Raiten, Daniel J; Northrop-Clewes, Christine A

    2017-01-01

    Background: The accurate estimation of iron deficiency is important in planning and implementing interventions. Ferritin is recommended as the primary measure of iron status, but interpretability is challenging in settings with infection and inflammation. Objective: We assessed the relation between ferritin concentrations and inflammation and malaria in preschool children (PSC) (age range: 6–59 mo) and women of reproductive age (WRA) (age range: 15–49 y) and investigated adjustment algorithms to account for these effects. Design: Cross-sectional data from 15 surveys for PSC (n = 27,865) and 8 surveys for WRA (24,844), from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and combined with the use of a meta-analysis. Several approaches were explored to estimate depleted iron stores (ferritin concentration inflammation and malaria settings as follows: 1) increase ferritin-concentration cutoff to 5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L; 3) apply arithmetic correction factors; and 4) use a regression correction approach. Results: Depleted iron-store estimates incrementally increased as CRP and AGP deciles decreased (4% compared with 30%, and 6% compared with 29% from highest compared with lowest CRP deciles for pooled PSC and WRA, respectively, with similar results for AGP). Depending on the approach used to adjust for inflammation (CRP plus AGP), the estimated prevalence of depleted iron stores increased by 7–25 and 2–8 absolute median percentage points for PSC and WRA, respectively, compared with unadjusted values. Adjustment for malaria in addition to CRP and AGP did not substantially change the estimated prevalence of depleted iron stores. Conclusions: Our results lend support for the use of internal regression correction to estimate the prevalence of depleted iron stores in regions with inflammation. This approach appears to mathematically reflect the linear

  8. GLP-1 nanomedicine alleviates gut inflammation.

    Science.gov (United States)

    Anbazhagan, Arivarasu N; Thaqi, Mentor; Priyamvada, Shubha; Jayawardena, Dulari; Kumar, Anoop; Gujral, Tarunmeet; Chatterjee, Ishita; Mugarza, Edurne; Saksena, Seema; Onyuksel, Hayat; Dudeja, Pradeep K

    2017-02-01

    The gut hormone, glucagon like peptide-1 (GLP-1) exerts anti-inflammatory effects. However, its clinical use is limited by its short half-life. Previously, we have shown that GLP-1 as a nanomedicine (GLP-1 in sterically stabilized phospholipid micelles, GLP-1-SSM) has increased in vivo stability. The current study was aimed at testing the efficacy of this GLP-1 nanomedicine in alleviating colonic inflammation and associated diarrhea in dextran sodium sulfate (DSS) induced mouse colitis model. Our results show that GLP-1-SSM treatment markedly alleviated the colitis phenotype by reducing the expression of pro-inflammatory cytokine IL-1β, increasing goblet cells and preserving intestinal epithelial architecture in colitis model. Further, GLP-1-SSM alleviated diarrhea (as assessed by luminal fluid) by increasing protein expression of intestinal chloride transporter DRA (down regulated in adenoma). Our results indicate that GLP-1 nanomedicine may act as a novel therapeutic tool in alleviating gut inflammation and associated diarrhea in inflammatory bowel disease (IBD). Published by Elsevier Inc.

  9. "TRP inflammation" relationship in cardiovascular system.

    Science.gov (United States)

    Numata, Tomohiro; Takahashi, Kiriko; Inoue, Ryuji

    2016-05-01

    Despite considerable advances in the research and treatment, the precise relationship between inflammation and cardiovascular (CV) disease remains incompletely understood. Therefore, understanding the immunoinflammatory processes underlying the initiation, progression, and exacerbation of many cardiovascular diseases is of prime importance. The innate immune system has an ancient origin and is well conserved across species. Its activation occurs in response to pathogens or tissue injury. Recent studies suggest that altered ionic balance, and production of noxious gaseous mediators link to immune and inflammatory responses with altered ion channel expression and function. Among plausible candidates for this are transient receptor potential (TRP) channels that function as polymodal sensors and scaffolding proteins involved in many physiological and pathological processes. In this review, we will first focus on the relevance of TRP channel to both exogenous and endogenous factors related to innate immune response and transcription factors related to sustained inflammatory status. The emerging role of inflammasome to regulate innate immunity and its possible connection to TRP channels will also be discussed. Secondly, we will discuss about the linkage of TRP channels to inflammatory CV diseases, from a viewpoint of inflammation in a general sense which is not restricted to the innate immunity. These knowledge may serve to provide new insights into the pathogenesis of various inflammatory CV diseases and their novel therapeutic strategies.

  10. The receptor RAGE: Bridging inflammation and cancer

    Directory of Open Access Journals (Sweden)

    Hess Jochen

    2009-05-01

    Full Text Available Abstract The receptor for advanced glycation end products (RAGE is a single transmembrane receptor of the immunoglobulin superfamily that is mainly expressed on immune cells, neurons, activated endothelial and vascular smooth muscle cells, bone forming cells, and a variety of cancer cells. RAGE is a multifunctional receptor that binds a broad repertoire of ligands and mediates responses to cell damage and stress conditions. It activates programs responsible for acute and chronic inflammation, and is implicated in a number of pathological diseases, including diabetic complications, stroke, atheriosclerosis, arthritis, and neurodegenerative disorders. The availability of Rage knockout mice has not only advanced our knowledge on signalling pathways within these pathophysiological conditions, but also on the functional importance of the receptor in processes of cancer. Here, we will summarize molecular mechanisms through which RAGE signalling contributes to the establishment of a pro-tumourigenic microenvironment. Moreover, we will review recent findings that provide genetic evidence for an important role of RAGE in bridging inflammation and cancer.

  11. [New inflammation modulator interleukins . Therapeutic implications].

    Science.gov (United States)

    Lupuşoru, Catălina Elena; Tarţău, Liliana; Ghiciuc, Cristina

    2002-01-01

    A lot of different leukocyte recruit soluble factors are implicated in both acute and chronic inflammatory processes with a higher expression of the cellular adhesion and chemoattraction molecules. Soluble factors implicated in these processes include: lipid inflammatory metabolites, arachydonic acid derivatives (prostaglandines, leucotrienes, lipoxines, PAF), the three soluble proteases waterfall events/substrates (coagulation, complement, kinines), nitric oxide, as well as cytokines implicated in acute or chronic inflammatory and cellular immune reactions. Recently, new inflammation modulator cytokines were described: IL-20, IL-21, IL-22 and IL-23. The aim of this work was to present some theoretical aspects regarding the biological effects of these new cytokines implicated in inflammation and the pharmacological influence of the processes mediated by them. Particularly IL-20 is implicated in psoriasis pathology. IL-21 and IL-15 are important in NK cells differentiation. IL-22 regulates the IL-4 production from Th2T cells. IL-23 stimulates IFN gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells.

  12. Heme on innate immunity and inflammation

    Directory of Open Access Journals (Sweden)

    Fabianno Ferreira Dutra

    2014-05-01

    Full Text Available Heme is an essential molecule expressed ubiquitously all through our tissues. Heme plays major functions in cellular physiology and metabolism as the prostetic group of diverse proteins. Once released from cells and from hemeproteins free heme causes oxidative damage and inflammation, thus acting as a prototypic damage-associated molecular pattern. In this context, free heme is a critical component of the pathological process of sterile and infectious hemolytic conditions including malaria, hemolytic anemias, ischemia-reperfusion and hemorrhage. The plasma scavanger proteins hemopexin and albumin reduce heme toxicity and are responsible for transporting free heme to intracellular compartments where it is catabolized by heme-oxygenase enzymes. Upon hemolysis or severe cellular damage the serum capacity to scavange heme may saturate and increase free heme to sufficient amounts to cause tissue damage in various organs. The mechanism by which heme causes reactive oxygen generation, activation of cells of the innate immune system and cell death are not fully understood. Although heme can directly promote lipid peroxidation by its iron atom, heme can also induce ROS generation and production of inflammatory mediators through the activation of selective signaling pathways. Heme activates innate immune cells such as macrophages and neutrophils through activation of innate immune receptors. The importance of these events has been demonstrated in infectious and non-infectious diseases models. In this review we will discuss the mechanisms behind heme-induced citotoxicity and inflammation and the consequences of these events on different tissues and diseases.

  13. Malondialdehyde epitopes as mediators of sterile inflammation.

    Science.gov (United States)

    Busch, Clara J; Binder, Christoph J

    2017-04-01

    Enhanced lipid peroxidation occurs during oxidative stress and results in the generation of lipid peroxidation end products such as malondialdehyde (MDA), which can attach to autologous biomolecules, thereby generating neo-self epitopes capable of inducing potentially undesired biological responses. Therefore, the immune system has developed mechanisms to protect from MDA epitopes by binding and neutralizing them through both cellular and soluble effectors. Here, we briefly discuss innate immune responses targeting MDA epitopes and their pro-inflammatory properties, followed by a review of physiological carriers of MDA epitopes that are relevant in homeostasis and disease. Then we discuss in detail the evidence for cellular responses towards MDA epitopes mainly in lung, liver and the circulation as well as signal transduction mechanisms and receptors implicated in the response to MDA epitopes. Last, we hypothesize on the role of MDA epitopes as mediators of inflammation in diseases and speculate on their contribution to disease pathogenesis. This article is part of a Special Issue entitled: Lipid modification and lipid peroxidation products in innate immunity and inflammation edited by Christoph J. Binder. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Environmental immune disruptors, inflammation and cancer risk

    Science.gov (United States)

    Thompson, Patricia A.; Khatami, Mahin; Baglole, Carolyn J.; Sun, Jun; Harris, Shelley; Moon, Eun-Yi; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Brown, Dustin; Colacci, Annamaria; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth; Woodrick, Jordan; Scovassi, Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Amedei, Amedeo; Hamid, Roslida A.; Lowe, Leroy; Guarnieri, Tiziana

    2015-01-01

    An emerging area in environmental toxicology is the role that chemicals and chemical mixtures have on the cells of the human immune system. This is an important area of research that has been most widely pursued in relation to autoimmune diseases and allergy/asthma as opposed to cancer causation. This is despite the well-recognized role that innate and adaptive immunity play as essential factors in tumorigenesis. Here, we review the role that the innate immune cells of inflammatory responses play in tumorigenesis. Focus is placed on the molecules and pathways that have been mechanistically linked with tumor-associated inflammation. Within the context of chemically induced disturbances in immune function as co-factors in carcinogenesis, the evidence linking environmental toxicant exposures with perturbation in the balance between pro- and anti-inflammatory responses is reviewed. Reported effects of bisphenol A, atrazine, phthalates and other common toxicants on molecular and cellular targets involved in tumor-associated inflammation (e.g. cyclooxygenase/prostaglandin E2, nuclear factor kappa B, nitric oxide synthesis, cytokines and chemokines) are presented as example chemically mediated target molecule perturbations relevant to cancer. Commentary on areas of additional research including the need for innovation and integration of systems biology approaches to the study of environmental exposures and cancer causation are presented. PMID:26106141

  15. Macrophages in intestinal homeostasis and inflammation

    Science.gov (United States)

    Bain, Calum C; Mowat, Allan McI

    2014-01-01

    The intestine contains the largest pool of macrophages in the body which are essential for maintaining mucosal homeostasis in the face of the microbiota and the constant need for epithelial renewal but are also important components of protective immunity and are involved in the pathology of inflammatory bowel disease (IBD). However, defining the biological roles of intestinal macrophages has been impeded by problems in defining the phenotype and origins of different populations of myeloid cells in the mucosa. Here, we discuss how multiple parameters can be used in combination to discriminate between functionally distinct myeloid cells and discuss the roles of macrophages during homeostasis and how these may change when inflammation ensues. We also discuss the evidence that intestinal macrophages do not fit the current paradigm that tissue-resident macrophages are derived from embryonic precursors that self-renew in situ, but require constant replenishment by blood monocytes. We describe our recent work demonstrating that classical monocytes constantly enter the intestinal mucosa and how the environment dictates their subsequent fate. We believe that understanding the factors that drive intestinal macrophage development in the steady state and how these may change in response to pathogens or inflammation could provide important insights into the treatment of IBD. PMID:24942685

  16. Inflammation and Hypertension: Are There Regional Differences?

    Directory of Open Access Journals (Sweden)

    Patricio López-Jaramillo

    2013-01-01

    Full Text Available Hypertension is a chronic disease with global prevalence and incidence rapidly increasing in low and medium income countries. The surveillance of cardiovascular risk factors, such as hypertension, is a global health priority in order to estimate the burden and trends, to appropriately direct resources, and to measure the effect of interventions. We propose here that the adoption of Western lifestyles in low and middle incomes countries has dramatically increased the prevalence of abdominal obesity, which is the main source of proinflammatory cytokines, and that the vascular systemic inflammation produced by adipose tissue contributes to the development of hypertension. The concentration of proinflammatory cytokines is higher in the Latin American population than that reported in developed countries, suggesting a higher susceptibility to develop systemic low-degree inflammation at a given level of abdominal obesity. These particularities are important to be considered when planning resources for health care programs. Moreover, studying these singularities may provide a better understanding of the causes of the burden of cardiovascular risk factors and the remarkable variability in the prevalence of these medical conditions within and between countries.

  17. Chemically induced mouse models of intestinal inflammation.

    Science.gov (United States)

    Wirtz, Stefan; Neufert, Clemens; Weigmann, Benno; Neurath, Markus F

    2007-01-01

    Animal models of intestinal inflammation are indispensable for our understanding of the pathogenesis of Crohn disease and ulcerative colitis, the two major forms of inflammatory bowel disease in humans. Here, we provide protocols for establishing murine 2,4,6-trinitro benzene sulfonic acid (TNBS)-, oxazolone- and both acute and chronic dextran sodium sulfate (DSS) colitis, the most widely used chemically induced models of intestinal inflammation. In the former two models, colitis is induced by intrarectal administration of the covalently reactive reagents TNBS/oxazolone, which are believed to induce a T-cell-mediated response against hapten-modified autologous proteins/luminal antigens. In the DSS model, mice are subjected several days to drinking water supplemented with DSS, which seems to be directly toxic to colonic epithelial cells of the basal crypts. The procedures for the hapten models of colitis and acute DSS colitis can be accomplished in about 2 weeks but the protocol for chronic DSS colitis takes about 2 months.

  18. Microbial Induction of Immunity, Inflammation And Cancer

    Directory of Open Access Journals (Sweden)

    Stephen John O'Keefe

    2011-01-01

    Full Text Available The human microbiota presents a highly active metabolic that influences the state of health of our gastrointestinal tracts as well as our susceptibility to disease. Although much of our initial microbiota is adopted from our mothers, its final composition and diversity is determined by environmental factors. Westernization has significantly altered our microbial function. Extensive experimental and clinical evidence indicates that the westernized diet, rich in animal products and low in complex carbohydrates, plus the overuse of antibiotics and underuse of breastfeeding, leads to a heightened inflammatory potential of the microbiota. Chronic inflammation leads to the expression of certain diseases in genetically predisposed individuals. Antibiotics and a ‘clean’ environment, termed the ‘hygiene hypothesis’, has been linked to the rise in allergy and inflammatory bowel disease, due to impaired beneficial bacterial exposure and education of the gut immune system, which comprises the largest immune organ within the body. The elevated risk of colon cancer is associated with the suppression of microbial fermentation and butyrate production, as butyrate provides fuel for the mucosa and is anti-inflammatory and anti-proliferative. This article will summarize the work to date highlighting the complicated and dynamic relationship between the gut microbiota and immunity, inflammation and carcinogenesis.

  19. Vulnerable Plaques, Inflammation and Newer Imaging Modalities

    Directory of Open Access Journals (Sweden)

    Bhatia V

    2003-01-01

    Full Text Available Currently, inflammation is considered to be the central player in the pathogenesis of atherosclerosis. It leads to the formation of multiple plaques in the arterial beds including coronary vasculature. Recent studies using the latest imaging techniques have shown that in patients with acute coronary syndromes (ACS multiple plaques are ruptured and have thrombus formation on them. Various factors make these plaques unstable, these include structural components of plaque like thin fibrous cap, high lipid content of the plaque core and inflammation, both localized and generalized. It has been shown that most of the ACS are caused by plaques causing non-critical stenosis as seen on traditional X-ray angiography. Also, the phenomenon of remodelling makes angiography a poor technique for plaque visualization. Hence newer modalities are required to identify these 'vulnerable plaques'. Intravascular ultrasound (IVUS, thermography and Magnetic Resonance Imaging (MRI are a few such promising techniques. Here we review the invasive and non-invasive modalities that can be helpful in the identification of these plaques before they become unstable and cause ACS, and also the available therapies to stabilize these plaques.

  20. Sphingolipid metabolism and obesity-induced inflammation

    Directory of Open Access Journals (Sweden)

    Se-Chan eKang

    2013-06-01

    Full Text Available Obesity is a metabolic disorder developed by overnutrition and a major cause for insulin resistance and cardiovascular events. Since adipose tissue is one of the major sites for the synthesis and secretion of cytokines, enlarged adipose tissue in obese condition alters inflammatory state leading to pathophysiological conditions such as type 2 diabetes and increased cardiovascular risk. A plausible theory for development of metabolic dysregulation is that obesity increases secretion of inflammatory cytokines from adipose tissue and causes a chronic inflammation in the whole body. Additionally accumulation of lipids in nonadipose tissues elevates the cellular levels of bioactive lipids that inhibit the signaling pathways implicated in metabolic regulation together with activated inflammatory response. Recent findings suggest that obesity-induced inflammatory response leads to modulation of sphingolipid metabolism and these bioactive lipids may function as mediators for increased risk of metabolic dysfunction. Importantly, elucidation of mechanism regarding sphingolipid metabolism and inflammatory disease will provide crucial information to development of new therapeutic strategies for the treatment of obesity-induced pathological inflammation.

  1. Systemic markers of inflammation in periodontitis.

    Science.gov (United States)

    Loos, Bruno G

    2005-11-01

    This literature review summarizes current knowledge on the systemic levels of selected markers of inflammation in periodontitis. From samples of peripheral blood the following cellular factors are discussed: total number of white blood cells, red blood cells, and thrombocytes. Further, plasma levels of acute-phase proteins, cytokines, and coagulation factors are reviewed. From the available literature it appears that the total numbers of leukocytes and plasma levels of C-reactive protein are consistently higher in periodontitis patients compared to healthy controls. Numbers of red blood cells and levels of hemoglobin are lower in periodontitis and there is a trend towards anemia of chronic disease. Most systemic markers of inflammation discussed in this review are also regarded as predictive markers for cardiovascular diseases. Therefore, changes in these markers in periodontitis may be part of the explanation why periodontitis is associated with cardiovascular diseases and/or cerebrovascular events in epidemiological studies. It is hypothesized that possibly daily episodes of a bacteremia originating from periodontal lesions are the cause for the changes in systemic markers in periodontitis; the cumulative size of all periodontal lesions in the untreated severe patient may amount to 15 to 20 cm2.

  2. An Update on Inflamm-Aging: Mechanisms, Prevention, and Treatment

    Directory of Open Access Journals (Sweden)

    Shijin Xia

    2016-01-01

    Full Text Available Inflamm-aging is a challenging and promising new branch of aging-related research fields that includes areas such as immunosenescence. Increasing evidence indicates that inflamm-aging is intensively associated with many aging diseases, such as Alzheimer’s disease, atherosclerosis, heart disease, type II diabetes, and cancer. Mounting studies have focused on the role of inflamm-aging in disease progression and many advances have been made in the last decade. However, the underlying mechanisms by which inflamm-aging affects pathological changes and disease development are still unclear. Here, we review studies of inflamm-aging that explore the concept, pathological features, mechanisms, intervention, and the therapeutic strategies of inflamm-aging in disease progression.

  3. Does Inflammation Mediate the Association Between Obesity and Insulin Resistance?

    Science.gov (United States)

    Adabimohazab, Razieh; Garfinkel, Amanda; Milam, Emily C; Frosch, Olivia; Mangone, Alexander; Convit, Antonio

    2016-06-01

    In adult obesity, low-grade systemic inflammation is considered an important step in the pathogenesis of insulin resistance (IR). The association between obesity and inflammation is less well established in adolescents. Here, we ascertain the importance of inflammation in IR among obese adolescents by utilizing either random forest (RF) classification or mediation analysis approaches. The inflammation balance score, composed of eight pro- and anti-inflammatory makers, as well as most of the individual inflammatory markers differed significantly between lean and overweight/obese. In contrast, adiponectin was the only individual marker selected as a predictor of IR by RF, and the balance score only revealed a medium-to-low importance score. Neither adiponectin nor the inflammation balance score was found to mediate the relationship between obesity and IR. These findings do not support the premise that low-grade systemic inflammation is a key for the expression of IR in the human. Prospective longitudinal studies should confirm these findings.

  4. Dietary Modulation of Inflammation-Induced Colorectal Cancer through PPARγ

    Directory of Open Access Journals (Sweden)

    Ashlee B. Carter

    2009-01-01

    Full Text Available Mounting evidence suggests that the risk of developing colorectal cancer (CRC is dramatically increased for patients with chronic inflammatory diseases. For instance, patients with Crohn's Disease (CD or Ulcerative Colitis (UC have a 12–20% increased risk for developing CRC. Preventive strategies utilizing nontoxic natural compounds that modulate immune responses could be successful in the suppression of inflammation-driven colorectal cancer in high-risk groups. The increase of peroxisome proliferator-activated receptor-γ (PPAR-γ expression and its transcriptional activity has been identified as a target for anti-inflammatory efforts, and the suppression of inflammation-driven colon cancer. PPARγ down-modulates inflammation and elicits antiproliferative and proapoptotic actions in epithelial cells. All of which may decrease the risk for inflammation-induced CRC. This review will focus on the use of orally active, naturally occurring chemopreventive approaches against inflammation-induced CRC that target PPARγ and therefore down-modulate inflammation.

  5. Injury, inflammation and the emergence of human specific genes

    Science.gov (United States)

    2016-07-12

    BIOMEDICAL HYPOTHESIS Injury, inflammation and the emergence of human-specific genes Andrew Baird, PhD; Todd Costantini, MD; Raul Coimbra, MD, PhD...medium, provided the original work is properly cited and is not used for commercial purposes. ABSTRACT In light of the central role of inflammation in...the biology of injury, namely infection, inflammation , and tissue repair and regene- ration. These genes include well-known anti-infection and human

  6. Sterile inflammation in acute liver injury: myth or mystery?

    OpenAIRE

    Woolbright, Benjamin L.; Jaeschke, Hartmut

    2015-01-01

    Inflammation during liver injury normally serves as a mechanism for cleaning up debris and as a stimulant for regeneration. However, aberrant levels of inflammation can provoke further liver injury and inhibit regeneration through the release of damaging reactive oxygen species. Considerable effort has gone into understanding the mechanisms that control the switch between healthy and pathological inflammation. The identification of a receptor system that detects damage-associated molecular pa...

  7. Inflammation activation and resolution in human tendon disease

    OpenAIRE

    Dakin, Stephanie G; Martinez, Fernando O; Yapp, Clarence; Wells, Graham; Oppermann, Udo; Dean, Benjamin JF; Smith, Richard DJ; Wheway, Kim; Watkins, Bridget; Roche, Lucy; Carr, Andrew J

    2015-01-01

    Improved understanding of the role of inflammation in tendon disease is required to facilitate therapeutic target discovery. We studied supraspinatus tendons from patients experiencing pain before and after surgical subacromial decompression treatment. Tendons were classified as having early, intermediate or advanced disease and inflammation was characterized through activation of pathways mediated by Interferon, NF-κB, glucocorticoid receptor and STAT-6. Inflammation signatures revealed expr...

  8. Activation and Resolution of Periodontal Inflammation and Its Systemic Impact

    OpenAIRE

    Hasturk, Hatice; Kantarci, Alpdogan

    2015-01-01

    Inflammation is a highly organized event impacting upon organs, tissues and biological systems. Periodontal diseases are characterized by dysregulation or dysfunction of resolution pathways of inflammation resulting in a failure of healing and a dominant chronic, progressive, destructive and predominantly unresolved inflammation. The biological consequences of inflammatory processes may be independent of the etiological agents such as trauma, microbial organisms and stress. The impact of the ...

  9. Inflammation and Oxidative Stress in Obesity-Related Glomerulopathy

    OpenAIRE

    Tang, Jinhua; Yan, Haidong; Zhuang, Shougang

    2012-01-01

    Obesity-related glomerulopathy is an increasing cause of end-stage renal disease. Obesity has been considered a state of chronic low-grade systemic inflammation and chronic oxidative stress. Augmented inflammation in adipose and kidney tissues promotes the progression of kidney damage in obesity. Adipose tissue, which is accumulated in obesity, is a key endocrine organ that produces multiple biologically active molecules, including leptin, adiponectin, resistin, that affect inflammation, and ...

  10. Inflammation and its resolution and the musculoskeletal system

    Directory of Open Access Journals (Sweden)

    Jiri Gallo

    2017-07-01

    The translational potential of this article: Understanding the mechanisms of inflammation and its resolution is therefore critical for the development of effective regenerative, and therapeutic strategies in orthopaedics.

  11. Muscle regeneration and inflammation in patients with facioscapulohumeral muscular dystrophy

    DEFF Research Database (Denmark)

    Hauerslev, S; Ørngreen, M C; Hertz, J M

    2013-01-01

    The aim of this study was to investigate whether inflammation and regeneration are prominent in mildly affected muscles of patients with facioscapulohumeral muscular dystrophy type 1A (FSHD1A). Inflammation in muscle has been suggested by MRI studies in patients with FSHD1A.......The aim of this study was to investigate whether inflammation and regeneration are prominent in mildly affected muscles of patients with facioscapulohumeral muscular dystrophy type 1A (FSHD1A). Inflammation in muscle has been suggested by MRI studies in patients with FSHD1A....

  12. Effects of intrauterine infection or inflammation on fetal lung development.

    Science.gov (United States)

    Westover, Alana J; Moss, Timothy J M

    2012-09-01

    1. Intrauterine infection or inflammation is common in cases of preterm birth. Preterm infants are at risk of acute respiratory distress as a result of lung immaturity; evidence of exposure to infection and/or inflammation before birth is associated with a reduced risk of neonatal respiratory distress syndrome (RDS). Experimentally induced intrauterine inflammation or infection in sheep causes a precocious increase in pulmonary surfactant in the preterm lungs that improves preterm lung function, consistent with the reduced risk of RDS in human infants exposed to infection and/or inflammation before birth. 2. The effects of intrauterine inflammation on fetal lung development appear to result from direct action of proinflammatory stimuli within the lungs rather than by systemic signals, such as the classical glucocorticoid-mediated lung maturation pathway. However, paracrine and/or autocrine production and/or metabolism of glucocorticoids in fetal lung tissue may occur as a result of inflammation-induced changes in the expression of 11β-hydroxysteroid dehydrogenase (types 1 and 2). 3. Likely candidates that mediate inflammation-induced surfactant production by the preterm lung include prostaglandin E₂ and/or other arachidonic acid metabolites. Intrauterine inflammation induces the expression of enzymes responsible for prostaglandin production in fetal lung tissue. Inhibition of prostaglandin production prevents, at least in part, the effects of inflammation on fetal lungs. 4. Our experiments are identifying mechanisms of surfactant production by the preterm lungs that may be exploited as novel therapies for preventing respiratory distress in preterm infants. Elucidation of the effects of inflammation on the fetal lungs and other organs will allow more refined approaches to the care of preterm infants exposed to inflammation in utero. Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.

  13. Maternal Obesity, Inflammation, and Developmental Programming

    Directory of Open Access Journals (Sweden)

    Stephanie A. Segovia

    2014-01-01

    Full Text Available The prevalence of obesity, especially in women of child-bearing age, is a global health concern. In addition to increasing the immediate risk of gestational complications, there is accumulating evidence that maternal obesity also has long-term consequences for the offspring. The concept of developmental programming describes the process in which an environmental stimulus, including altered nutrition, during critical periods of development can program alterations in organogenesis, tissue development, and metabolism, predisposing offspring to obesity and metabolic and cardiovascular disorders in later life. Although the mechanisms underpinning programming of metabolic disorders remain poorly defined, it has become increasingly clear that low-grade inflammation is associated with obesity and its comorbidities. This review will discuss maternal metainflammation as a mediator of programming in insulin sensitive tissues in offspring. Use of nutritional anti-inflammatories in pregnancy including omega 3 fatty acids, resveratrol, curcumin, and taurine may provide beneficial intervention strategies to ameliorate maternal obesity-induced programming.

  14. The Role of Inflammation in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Norbert eMüller

    2015-10-01

    Full Text Available AbstractHigh levels of pro-inflammatory substances such as cytokines have been described in the blood and cerebrospinal fluid of schizophrenia patients. Animal models of schizophrenia show that under certain conditions an immune disturbance during early life, such as an infection-triggered immune activation, might trigger lifelong increased immune reactivity. A large epidemiological study clearly demonstrated that severe infections and autoimmune disorders are risk factors for schizophrenia. Genetic studies have shown a strong signal for schizophrenia on chromosome 6p22.1, in a region related to the human leucocyte antigen (HLA system and other immune functions. Another line of evidence demonstrates that chronic (disstress is associated with immune activation. The vulnerability-stress-inflammation model of schizophrenia includes the contribution of stress on the basis of increased genetic vulnerability for the pathogenesis

  15. Toll-Like Receptors and Myocardial Inflammation

    Directory of Open Access Journals (Sweden)

    Yan Feng

    2011-01-01

    Full Text Available Toll-like receptors (TLRs are a member of the innate immune system. TLRs detect invading pathogens through the pathogen-associated molecular patterns (PAMPs recognition and play an essential role in the host defense. TLRs can also sense a large number of endogenous molecules with the damage-associated molecular patterns (DAMPs that are produced under various injurious conditions. Animal studies of the last decade have demonstrated that TLR signaling contributes to the pathogenesis of the critical cardiac conditions, where myocardial inflammation plays a prominent role, such as ischemic myocardial injury, myocarditis, and septic cardiomyopathy. This paper reviews the animal data on (1 TLRs, TLR ligands, and the signal transduction system and (2 the important role of TLR signaling in these critical cardiac conditions.

  16. Kallikrein 5-Mediated Inflammation in Rosacea

    Science.gov (United States)

    Two, Aimee M.

    2014-01-01

    Rosacea is a chronic inflammatory condition of facial skin estimated to affect more than 16 million Americans. Although the pathogenesis of rosacea is not fully understood, recent evidence in vitro as well as in vivo has supported the role of increased levels of the trypsin-like serine protease, kallikrein 5, in initiating an augmented inflammatory response in rosacea. The increase in the quantity and magnitude of biological activity of kallikrein 5 leads to production of greater quantities of cathelicidin (LL-37), an antimicrobial peptide associated with increases in innate cutaneous inflammation, vasodilation, and vascular proliferation, all of which are characteristic features of rosacea. In this article, the authors review the literature supporting the role of kallikrein 5 in the pathophysiology of rosacea, including how therapeutic interventions modulate the effects of kallikrein 5, thus providing further support for this pathophysiological model that at least partially explains many of the clinical features of cutaneous rosacea. PMID:24563692

  17. Increase in gingival inflammation under academic stress.

    Science.gov (United States)

    Deinzer, R; Rüttermann, S; Möbes, O; Herforth, A

    1998-05-01

    Several correlational questionnaire studies have observed a positive relationship between psychological stress and periodontal diseases. This paper analyses the effects of academic stress on periodontal health in a prospective quasi-experimental design. 26 medical students participating in a major exam and the same number of medical students not participating in any exam throughout the study period volunteered for the study. Bleeding on probing was assessed 4 weeks prior to the exam period (baseline) and at the last day of the exam. Severe deterioration in gingival health from baseline to the last exam day were observed more frequently in exam students than in controls (p=0.014). 6 exam students but only 1 control person developed a severe gingivitis at at least one formerly healthy tooth throughout the study period. These results further support the hypothesis that psychological stress is a significant risk factor for periodontal inflammation. Future studies should examine factors mediating this relationship.

  18. [Inflammation and acute pharyngo-tonsillitis].

    Science.gov (United States)

    Pessey, J J

    1. Despite several studies, it has been impossible to establish a correlation between bacteriological and clinical findings in erythematous pultaceous sore throat. 2. Antibiotics should be prescribed for group A streptococcal sore throat alone. 3. In acute tonsilitis, inflammation is perfectly proportional to infection; 4. Their extremely important role in the pathogenesis of different inflammatory processes has been demonstrated in acute tonsilitis. 5. Based on the fact that no clinical argument can confirm or infirm the streptococcal cause, it is recommended to use a rapid diagnostic test in all adults or children with sore throat. 6. No data are available demonstrating the benefit of non-steroidal antiinflammatory drugs at antiinflammatory doses or of general corticosteroid treatment of acute sore throat. Nevertheless, in non-A hemolytic streptococcal where antibiotic treatment is not indicated, wouldn't it be useful to prescribe symptomatic antiinflammatory treatment?

  19. Thyroid Hormones, Oxidative Stress, and Inflammation

    Directory of Open Access Journals (Sweden)

    Antonio Mancini

    2016-01-01

    Full Text Available Inflammation and oxidative stress (OS are closely related processes, as well exemplified in obesity and cardiovascular diseases. OS is also related to hormonal derangement in a reciprocal way. Among the various hormonal influences that operate on the antioxidant balance, thyroid hormones play particularly important roles, since both hyperthyroidism and hypothyroidism have been shown to be associated with OS in animals and humans. In this context, the nonthyroidal illness syndrome (NTIS that typically manifests as reduced conversion of thyroxine (T4 to triiodothyronine (T3 in different acute and chronic systemic conditions is still a debated topic. The pathophysiological mechanisms of this syndrome are reviewed, together with the roles of deiodinases, the enzymes responsible for the conversion of T4 to T3, in both physiological and pathological situations. The presence of OS indexes in NTIS supports the hypothesis that it represents a condition of hypothyroidism at the tissue level and not only an adaptive mechanism to diseases.

  20. Oxidative stress, inflamm-aging and immunosenescence.

    Science.gov (United States)

    Cannizzo, Elvira S; Clement, Cristina C; Sahu, Ranjit; Follo, Carlo; Santambrogio, Laura

    2011-10-19

    Immunosenescence is characterized by a decreased ability of the immune system to respond to foreign antigens, as well as a decreased ability to maintain tolerance to self-antigens. This results in an increased susceptibility to infection and cancer and reduced responses to vaccination [1-5]. The mechanisms underlying immunosenescence comprise a series of cellular and molecular events involving alteration of several biochemical pathways and different cellular populations, and for the most part our understanding of these molecular mechanisms is still fragmentary. In this review we will focus on the process of senescence associated with oxidative stress, in particular how protein oxidation alters the functionality of immune cells and how oxidative stress contributes to a chronic inflammatory process often referred as inflamm-aging. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Systemic Treatments for Noninfectious Vitreous Inflammation

    Directory of Open Access Journals (Sweden)

    Angela Jiang

    2013-01-01

    Full Text Available Vitreous inflammation, or vitritis, may result from many causes, including both infectious and noninfectious, including rheumatologic and autoimmune processes. Vitritis is commonly vision threatening and has serious sequelae. Treatment is frequently challenging, but, today, there are multiple methods of systemic treatment for vitritis. These categories include corticosteroids, antimetabolites, alkylating agents, T-cell inhibitors/calcineurin inhibitors, and biologic agents. These treatment categories were reviewed last year, but, even over the course of just a year, many therapies have made progress, as we have learned more about their indications and efficacy. We discuss here discoveries made over the past year on both existing and new drugs, as well as reviewing mechanisms of action, clinical dosages, specific conditions that are treated, adverse effects, and usual course of treatment for each class of therapy.

  2. Maternal obesity, inflammation, and developmental programming.

    Science.gov (United States)

    Segovia, Stephanie A; Vickers, Mark H; Gray, Clint; Reynolds, Clare M

    2014-01-01

    The prevalence of obesity, especially in women of child-bearing age, is a global health concern. In addition to increasing the immediate risk of gestational complications, there is accumulating evidence that maternal obesity also has long-term consequences for the offspring. The concept of developmental programming describes the process in which an environmental stimulus, including altered nutrition, during critical periods of development can program alterations in organogenesis, tissue development, and metabolism, predisposing offspring to obesity and metabolic and cardiovascular disorders in later life. Although the mechanisms underpinning programming of metabolic disorders remain poorly defined, it has become increasingly clear that low-grade inflammation is associated with obesity and its comorbidities. This review will discuss maternal metainflammation as a mediator of programming in insulin sensitive tissues in offspring. Use of nutritional anti-inflammatories in pregnancy including omega 3 fatty acids, resveratrol, curcumin, and taurine may provide beneficial intervention strategies to ameliorate maternal obesity-induced programming.

  3. Group differences in proneness to inflammation.

    Science.gov (United States)

    Pennington, Renee; Gatenbee, Chandler; Kennedy, Brett; Harpending, Henry; Cochran, Gregory

    2009-12-01

    All humans are primarily descendants from a diaspora out of Africa approximately 50,000 years ago although there are some indications of admixture with local populations of archaic humans outside Africa. The burden of infectious disease is greater in tropical Africa than elsewhere on earth in historic times, and it was less outside Africa, especially in the New World where passage through the Beringian filter kept many Old World parasites from entering the New World with humans. As a consequence we expect that the immune system, especially susceptibility to inflammation, will be "tuned up" in people with recent tropical African ancestry, intermediate in people of European and Asian ancestry, and perhaps "tuned down" in people of Native American ancestry. We suggest that evolved responses to different pathogen burdens among geographic groups may contribute to higher rates of inflammatory disease in modern people.

  4. Obesity, inflammation, and the gut microbiota.

    Science.gov (United States)

    Cox, Amanda J; West, Nicholas P; Cripps, Allan W

    2015-03-01

    As the prevalence of obesity and associated disease continues to rise and concerns for the spiralling economic and social costs also escalate, innovative management strategies beyond primary prevention and traditional lifestyle interventions are urgently needed. The biological basis of disease is one avenue for further exploration in this context. Several key inflammatory markers have been consistently associated with both obesity and risk of adverse outcomes in obesity-associated diseases, which suggests that a persistent, low-grade, inflammatory response is a potentially modifiable risk factor. In this Review, we provide evidence supporting perturbation of the intestinal microbiota and changes in intestinal permeability as potential triggers of inflammation in obesity. Further characterisation of the mechanisms underpinning the triggers of such inflammatory responses in overweight and obese individuals could offer unique opportunities for intervention strategies to help ameliorate the risk of obesity-associated disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Inflammation, depression and dementia: are they connected?

    Science.gov (United States)

    Leonard, Brian E

    2007-10-01

    Chronic inflammation is now considered to be central to the pathogenesis not only of such medical disorders as cardiovascular disease, multiple sclerosis, diabetes and cancer but also of major depression. If chronic inflammatory changes are a common feature of depression, this could predispose depressed patients to neurodegenerative changes in later life. Indeed there is now clinical evidence that depression is a common antecedent of Alzheimer's disease and may be an early manifestation of dementia before the cognitive declines becomes apparent. This review summarises the evidence that links chronic low grade inflammation with changes in brain structure that could precipitate neurodegenerative changes associated with Alzheimer's disease and other dementias. For example, neuronal loss is a common feature of major depression and dementia. It is hypothesised that the progress from depression to dementia could result from the activation of macrophages in the blood, and microglia in the brain, that release pro-inflammatory cytokines. Such cytokines stimulate a cascade of inflammatory changes (such as an increase in prostaglandin E2, nitric oxide in addition to more pro-inflammatory cytokines) and a hypersecretion of cortisol. The latter steroid inhibits protein synthesis thereby reducing the synthesis of neurotrophic factors and preventing reairto damages neuronal networks. In addition, neurotoxic end products of the tryptophan-kynurenine pathway, such as quinolinic acid, accumulate in astrocytes and neurons in both depression and dementia. Thus increased neurodegeneration, reduced neuroprotection and neuronal repair are common pathological features of major depression and dementia. Such changes may help to explain why major depression is a frequent prelude to dementia in later life.

  6. PROGRESSION VARIANTS OF CHRONIC SYSTEMIC INFLAMMATION

    Directory of Open Access Journals (Sweden)

    E. Y. Gusev

    2009-01-01

    Full Text Available Abstract. Fourteen groups of patients have been investigated and divided into 2 classes. The first class included the following cohorts of patients: relatively healthy persons, age 18 to 55 yrs (n = 50; elderly persons 60 yrs old, as well as senior persons (n = 22; persons with chronic adnexitis, women in their 1st trimester of pregnancy (n = 16; climacteric syndrome (n = 16; autoimmune thyroiditis (n = 29. The second class of patients included following cohorts: elderly persons with chronic cardiac insufficiency (CCI II-III stage (n=49; valvular cardiac disease (rheumatism, n = 15; psoriatic arthritis (n = 12; reactive arthritis (n = 17; antiphospholipid syndrome, a sub-group in the 1st trimester of pregnancy (n = 5; systemic lupus erythematosus (n=49; decompensated atherosclerosis of femoral artery (n = 38; end-stage renal disease (n = 42. Plasma cytokines (TNFαα, IL-6, IL-8, IL-10, acute-phase C-reactive protein (CRP, cortisol, troponin I, myoglobin, D-dimers, interleukin-2 soluble receptor (IL-2sR, and eosinophil cationic protein (ECP were determined in all the patients, by means of immune chemiluminescent technique (Immulite; Siemens Medical Solutions Diagnostics, USA. The integral indices of systemic inflammatory reaction (SIR have been calculated, i.e., a Reactivity Coefficient (RC and a Reactivity Level (RL. In the patients belonging to Class 1 cohorts, an absence of chronic systemic inflammation features was revealed, despite of some signs of systemic inflammatory response. Meanwhile, a majority of Class 2 patients have shown the signs of chronic systemic inflammation stage I to III.

  7. Parstatin Suppresses Ocular Neovascularization and Inflammation

    Science.gov (United States)

    Huang, Hu; Vasilakis, Panagiotis; Zhong, Xiufeng; Shen, Ji-Kui; Geronatsiou, Katerina; Papadaki, Helen; Maragoudakis, Michael E.; Gartaganis, Sotirios P.; Vinores, Stanley A.

    2010-01-01

    Purpose. Parstatin is a 41-mer peptide formed by proteolytic cleavage on activation of the PAR1 receptor. The authors recently showed that parstatin is a potent inhibitor of angiogenesis. The purpose of the present study was to evaluate the therapeutic effect of parstatin on ocular neovascularization. Methods. Choroidal neovascularization was generated in mice using laser-induced rupture of Bruch's membrane and was assessed after 14 days after perfusion of FITC-dextran. Oxygen-induced retinal neovascularization was established in neonatal mice by exposing them to 75% O2 at postnatal day (P)7 for 5 days and then placing them in room air for 5 days. Evaluation was performed on P17 after staining with anti-mouse PECAM-1. The effect of parstatin was tested after intravitreal administration. The effects of subconjunctival-injected parstatin on corneal neovascularization and inflammation in rats were assessed 7 days after chemical burn-induced corneal neovascularization. Retinal leukostasis in mice was assessed after perfusion with FITC-conjugated concanavalin A. Results. Parstatin potently inhibited choroidal neovascularization with an IC50 of approximately 3 μg and a maximum inhibition of 59% at 10 μg. Parstatin suppressed retinal neovascularization with maximum inhibition of 60% at 3 μg. Ten-microgram and 30-μg doses appeared to be toxic to the neonatal retina. Subconjunctival parstatin inhibited corneal neovascularization, with 200 μg the most effective dose (59% inhibition). In addition, parstatin significantly inhibited corneal inflammation and VEGF-induced retinal leukostasis. In all models tested, scrambled parstatin was without any significant effect. Conclusions. Parstatin is a potent antiangiogenic agent of ocular neovascularization and may have clinical potential in the treatment of angiogenesis-related ocular disorders. PMID:20538980

  8. Heme oxygenase-1, oxidation, inflammation and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jesus A Araujo

    2012-07-01

    Full Text Available Atherosclerosis is an inflammatory process of the vascular wall characterized by the infiltration of lipids and inflammatory cells. Oxidative modifications of infiltrating low density lipoproteins and induction of oxidative stress play a major role in lipid retention in the vascular wall, uptake by macrophages and generation of foam cells, a hallmark of this disorder. The vasculature has a plethora of protective resources against oxidation and inflammation, many of them regulated by the Nrf2 transcription factor. Heme oxygenase-1 (HO-1 is a Nrf2-regulated gene that plays a critical role in the prevention of vascular inflammation. It is the inducible isoform of heme oxygenase, responsible for the oxidative cleavage of heme groups leading to the generation of biliverdin, carbon monoxide and release of ferrous iron. HO-1 has important antioxidant, antiinflammatory, antiapoptotic, antiproliferative and immunomodulatory effects in vascular cells, most of which play a significant role in the protection against atherogenesis. HO-1 may also be an important feature in macrophage differentiation and polarization to certain subtypes. The biological effects of HO-1 are largely attributable to its enzymatic activity, which can be conceived as a system with three arms of action, corresponding to its three enzymatic byproducts. HO-1 mediated vascular protection may be due to a combination of systemic and vascular local effects. It is usually expressed at low levels but can be highly upregulated in the presence of several proatherogenic stimuli. The HO-1 system is amenable for use in the development of new therapies, some of them currently under experimental and clinical trials. Interestingly, in contrast to the HO-1 antiatherogenic actions, the expression of its transcriptional regulator Nrf2 leads to proatherogenic effects instead. This article reviews the evidence that supports the antiatherogenic role of HO-1, potential pathways and mechanisms mediating

  9. Endotoxins and inflammation in hemodialysis patients.

    Science.gov (United States)

    El-Koraie, Ahmed F; Naga, Yasmine S; Saaran, Amina M; Farahat, Nahla G; Hazzah, Walaa A

    2013-07-01

    Long-term endotoxin challenge may promote frequent complications in dialysis patients, namely malnutrition, chronic inflammation, and atherosclerosis, which are recognized as the so-called MIA syndrome. Circulating soluble vascular cell adhesion molecule-1 (sVCAM-1) levels may be used to determine the stage of atherosclerosis. This study aimed to assess endotoxin level in hemodialysis (HD) patients and its role in inducing inflammation. The study was conducted on 50 HD patients, chosen from four dialysis centers in Alexandria. Serum blood samples were collected for the determination of albumin and C-reactive protein (CRP), and whole blood samples were used for the measurement of hemoglobin level. A heparinized whole blood sample was taken postdialysis for endotoxin assay by limulus amebocyte lysate test, and in addition to sVCAM-1 was estimated using enzyme-linked immunosorbent assay. The mean endotoxin level was 76.30 pg/mL;80% exhibited values higher than 60 pg/mL. Half the studied patients had CRP values that exceeded the upper limit of the laboratory reference range (endotoxin and CRP levels (r = 0.47, P = 0.001). The mean pre-HD level of VCAM was 1851.00 ng/mL, while the mean post-HD level was 2829.00 ng/mL with statistically significant correlation (r = 0.354, P = 0.012) and it also correlated significantly with endotoxin as well as CRP levels. Endotoxemia may play an important role in the aggravation of endothelial dysfunction in HD patients as indicated by the post-HD rise in sVCAM-1. © 2012 The Authors. Hemodialysis International © 2012 International Society for Hemodialysis.

  10. Inhibition of vascular response in inflammation by crude aqueous ...

    African Journals Online (AJOL)

    Background: The root bark extract of Zanthoxylum xanthozyloides is used in folklore medicine in Ghana and Nigeria to treat inflammation. A previous pharmacological study confirmed the anti-inflammatory activity of the extract. Objective: To study the effect of the extract on vascular response in inflammation. Method: The ...

  11. Oral inflammatory diseases and systemic inflammation: role of the macrophage.

    Science.gov (United States)

    Hasturk, Hatice; Kantarci, Alpdogan; Van Dyke, Thomas E

    2012-01-01

    Inflammation is a complex reaction to injurious agents and includes vascular responses, migration, and activation of leukocytes. Inflammation starts with an acute reaction, which evolves into a chronic phase if allowed to persist unresolved. Acute inflammation is a rapid process characterized by fluid exudation and emigration of leukocytes, primarily neutrophils, whereas chronic inflammation extends over a longer time and is associated with lymphocyte and macrophage infiltration, blood vessel proliferation, and fibrosis. Inflammation is terminated when the invader is eliminated, and the secreted mediators are removed; however, many factors modify the course and morphologic appearance as well as the termination pattern and duration of inflammation. Chronic inflammatory illnesses such as diabetes, arthritis, and heart disease are now seen as problems that might have an impact on the periodontium. Reciprocal effects of periodontal diseases are potential factors modifying severity in the progression of systemic inflammatory diseases. Macrophages are key cells for the inflammatory processes as regulators directing inflammation to chronic pathological changes or resolution with no damage or scar tissue formation. As such, macrophages are involved in a remarkably diverse array of homeostatic processes of vital importance to the host. In addition to their critical role in immunity, macrophages are also widely recognized as ubiquitous mediators of cellular turnover and maintenance of extracellular matrix homeostasis. In this review, our objective is to identify macrophage-mediated events central to the inflammatory basis of chronic diseases, with an emphasis on how control of macrophage function can be used to prevent or treat harmful outcomes linked to uncontrolled inflammation.

  12. Gallium-labelled peptides for imaging of inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Roivainen, Anne [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); University of Turku, Turku Center for Disease Modeling, Turku (Finland); Jalkanen, Sirpa [University of Turku, MediCity Research Laboratory, Turku (Finland); University of Turku, Department of Medical Microbiology and Immunology, Turku (Finland); Nanni, Cristina [Azienda Ospedaliero-Universitaria S.Orsola Malpighi, UO Medicina Nucleare, Bologna (Italy)

    2012-02-15

    Inflammation plays a major role in the development of many diseases. This review article summarizes recent research in the field of in vivo imaging of inflammation. Novel methodologies using PET with {sup 68}Ga peptides targeting, for example, vascular adhesion protein 1 are discussed. (orig.)

  13. Characterization of inflammation in COPD : clinical and experimental approach

    NARCIS (Netherlands)

    Vernooy, J.H.J.

    2003-01-01

    Chronic inflammation is an important feature of COPD. This inflammatory response is not restricted to the local compartment - including airways, lung parenchyma, and pulmonary vasculature - but is also present in the circulation. However, the origin of the systemic inflammation present in COPD

  14. Voriconazole metabolism is influenced by severe inflammation : a prospective study

    NARCIS (Netherlands)

    Veringa, Anette; ter Avest, Mendy; Span, Lambert F. R.; van den Heuvel, Edwin R.; Touw, Daan J.; Zijlstra, Jan G.; Kosterink, Jos G. W.; van der Werf, Tjip S.; Alffenaar, Jan-Willem C.

    Background: During an infection or inflammation, several drug-metabolizing enzymes in the liver are downregulated, including cytochrome P450 iso-enzymes. Since voriconazole is extensively metabolized by cytochrome P450 iso-enzymes, the metabolism of voriconazole can be influenced during inflammation

  15. Treatment of orbital inflammation with rituximab in Wegener's granulomatosis

    DEFF Research Database (Denmark)

    Baslund, Bo; Wiencke, Anne Katrine; Rasmussen, Niels

    2012-01-01

    OBJECTIVES: To study the efficacy of rituximab therapy for the treatment of orbital inflammation in patients with Wegener's granulomatosis (WG). METHODS: Ten WG patients with orbital inflammation were included in this case-series. None had symptoms suggestive of extra-orbital disease activity...

  16. The Role of Brain Inflammation in Epileptogenesis in TSC

    Science.gov (United States)

    2014-07-01

    future challenges. Epilepsia 2007;48:617- 630. 2. Ravizza T, Balosso S, Vezzani A. Inflammation and prevention of epileptogenesis. Neurosci Lett...development. Neurobiol Dis 2006;24:128-143. 7. Aronica E, Crino PB. Inflammation in epilepsy: clinical observations. Epilepsia 2011;52(Suppl.3);26

  17. Inflammation. Courseware Evaluation for Vocational and Technical Education.

    Science.gov (United States)

    Yarbrough, Stephen

    This courseware evaluation rates the "Inflammation" program developed by Lane Community College in Eugene, Oregon. (This program--not contained in this document--introduces students to the possible causes, signs, and protective benefits of inflammation.) Part A describes the program in terms of subject area (allied health, nursing), and…

  18. Inflammation Effects on Motivation and Motor Activity: Role of Dopamine.

    Science.gov (United States)

    Felger, Jennifer C; Treadway, Michael T

    2017-01-01

    Motivational and motor deficits are common in patients with depression and other psychiatric disorders, and are related to symptoms of anhedonia and motor retardation. These deficits in motivation and motor function are associated with alterations in corticostriatal neurocircuitry, which may reflect abnormalities in mesolimbic and mesostriatal dopamine (DA). One pathophysiologic pathway that may drive changes in DAergic corticostriatal circuitry is inflammation. Biomarkers of inflammation such as inflammatory cytokines and acute-phase proteins are reliably elevated in a significant proportion of psychiatric patients. A variety of inflammatory stimuli have been found to preferentially target basal ganglia function to lead to impaired motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal neural responses to reward anticipation, decreased DA and DA metabolites in cerebrospinal fluid, and decreased availability, and release of striatal DA, all of which correlated with symptoms of reduced motivation and/or motor retardation. Importantly, inflammation-associated symptoms are often difficult to treat, and evidence suggests that inflammation may decrease DA synthesis and availability, thus circumventing the efficacy of standard pharmacotherapies. This review will highlight the impact of administration of inflammatory stimuli on the brain in relation to motivation and motor function. Recent data demonstrating similar relationships between increased inflammation and altered DAergic corticostriatal circuitry and behavior in patients with major depressive disorder will also be presented. Finally, we will discuss the mechanisms by which inflammation affects DA neurotransmission and relevance to novel therapeutic strategies to treat reduced motivation and motor symptoms in patients with high inflammation.

  19. Neutrophilic inflammation in asthma: mechanisms and therapeutic considerations.

    Science.gov (United States)

    Chang, Hun Soo; Lee, Tae-Hyeong; Jun, Ji Ae; Baek, Ae Rin; Park, Jong-Sook; Koo, So-My; Kim, Yang-Ki; Lee, Ho Sung; Park, Choon-Sik

    2017-01-01

    Neutrophilic airway inflammation represents a pathologically distinct form of asthma and frequently appears in symptomatic adulthood asthmatics. However, clinical impacts and mechanisms of the neutrophilic inflammation have not been thoroughly evaluated up to date. Areas covered: Currently, distinct clinical manifestations, triggers, and molecular mechanisms of the neutrophilic inflammation (namely Toll-like receptor, Th1, Th17, inflammasome) are under investigation in asthma. Furthermore, possible role of the neutrophilic inflammation is being investigated in respect to the airway remodeling. We searched the related literatures published during the past 10 years on the website of Pub Med under the title of asthma and neutrophilic inflammation in human. Expert commentary: Epidemiologic and experimental studies have revealed that the neutrophilic airway inflammation is induced by a wide variety of stimuli including ozone, particulate matters, cigarette smoke, occupational irritants, endotoxins, microbial infection and colonization, and aeroallergens. These triggers provoke diverse immune and inflammatory responses leading to progressive and sometimes irreversible airway obstruction. Clinically, neutrophilic airway inflammation is frequently associated with severe asthma and poor response to glucocorticoid therapy, indicating the need for other treatment strategies. Accordingly, therapeutics will be targeted against the main mediators behind the underlying molecular mechanisms of the neutrophilic inflammation.

  20. Low grade inflammation as measured by levels of YKL-40

    DEFF Research Database (Denmark)

    Rathcke, Camilla Noelle; Raymond, Ilan; Kistorp, Caroline

    2010-01-01

    BACKGROUND: Low grade inflammation is of pathogenic importance in the development of cardiovascular disease (CVD) and type 2 diabetes. The inflammation marker YKL-40 correlates with insulin resistance and is highly expressed in atherosclerotic plaques. We aimed to investigate whether YKL-40 could...

  1. The relationship between inflammation and the coagulation system

    NARCIS (Netherlands)

    Choi, Goda; Schultz, Marcus J.; Levi, Marcel; van der Poll, Tom

    2006-01-01

    Inflammation and coagulation play pivotal roles in host defence. As phylogenetically old responses, there is extensive cross-talk between inflammation and coagulation in enabling an adequate immune response against potentially injurious stimuli. Immune cells are important in the initiation of

  2. Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation

    NARCIS (Netherlands)

    Daemen, M. A.; van 't Veer, C.; Denecker, G.; Heemskerk, V. H.; Wolfs, T. G.; Clauss, M.; Vandenabeele, P.; Buurman, W. A.

    1999-01-01

    Ischemia followed by reperfusion leads to severe organ injury and dysfunction. Inflammation is considered to be the most important cause of tissue injury in organs subjected to ischemia. The mechanism that triggers inflammation and organ injury after ischemia remains to be elucidated, although

  3. Network-based characterization of inflammation biomarkers, phytochemicals and disease

    Science.gov (United States)

    Chronic inflammation is often a major contributor to the onset and progression of cardiometabolic dysfunction. Whether through effects on the inflammatory response system or independent of inflammation, plant-derived polyphenols comprise a micro-nutrient class important in cardiovascular disease and...

  4. Acidic Chitinase Limits Allergic Inflammation and Promotes Intestinal Nematode Expulsion

    Science.gov (United States)

    Acidic mammalian chitinase (AMCase) is stereotypically induced during mammalian immune responses to helminths and allergens—yet, its precise role in immunity and inflammation is unclear. Here we show that in the lung, genetic ablation of AMCase failed to diminish type 2 inflammation against helmint...

  5. Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation

    NARCIS (Netherlands)

    Hoeger, S.; Bergstraesser, C.; Selhorst, J.; Fontana, J.; Birck, R.; Waldherr, R.; Beck, G.; Sticht, C.; Seelen, M. A.; van Son, W. J.; Leuvenink, H.; Ploeg, R.; Schnuelle, P.; Yard, B. A.

    Because the vagus nerve is implicated in control of inflammation, we investigated if brain death (BD) causes impairment of the parasympathetic nervous system, thereby contributing to inflammation. BD was induced in rats. Anaesthetised ventilated rats (NBD) served as control. Heart rate variability

  6. Bakery flour dust exposure causes non-allergic inflammation and enhances allergic airway inflammation in mice.

    Science.gov (United States)

    Marraccini, P; Brass, D M; Hollingsworth, J W; Maruoka, S; Garantziotis, S; Schwartz, D A

    2008-09-01

    Baker's asthma is one of the most commonly reported occupational lung diseases in countries where fresh bread is baked daily in large quantities, and is characterized by rhinitis, bronchial hyperresponsiveness, and reversible airflow obstruction. Epidemiological studies have identified pre-existing atopy as an important risk factor for developing baker's asthma, yet the aetiology and pathogenesis of baker's asthma remain poorly understood. We sought to develop a mouse model of baker's asthma that could be used to characterize the development and progression of baker's asthma. We were unable to sensitize mice to bakery flour dust or flour dust extract. We assessed total inflammatory cells, cellular differential, total serum IgE and the pro-inflammatory cytokine response to oropharyngeally instilled bakery flour dust or flour dust extract by itself or in the context of ovalbumin (OVA) sensitization and challenge. Both bakery flour dust and flour dust extract consistently elicited a neutrophilic inflammation in a Toll-like receptor 4-independent manner; suggesting that endotoxin is not playing a role in the inflammatory response to flour dust. Moreover, bakery flour dust and dust extract significantly enhance the inflammatory response in OVA-sensitized and challenged mice. Bakery flour dust and flour dust extract are strongly pro-inflammatory and can cause non-allergic airway inflammation and can enhance allergen-mediated airway inflammation.

  7. Psychosocial distress and inflammation: Which way does causality flow?

    Science.gov (United States)

    Das, Aniruddha

    2016-12-01

    This study queried causal direction in linkages of inflammation with psychosocial distress. Data were from the 2005-2006 and 2010-2011 waves of the U.S. National Social Life, Health, and Aging Project. Inflammation was indicated by C-reactive protein, and distress by depression, anxiety, as well as stress. Autoregressive cross-lagged panel models were used to examine causal direction. Rather than being an outcome of psychosocial distress, inflammation was a predictor of it. Linkages were gender differentiated, with inflammation seeming to induce depression among men but stress among women. Contrary to previous literature, inflammation may not be a mechanism through which psychosocial distress gets "under the skin" to cause cardiovascular and metabolic issues. Rather, it may be a node through which social pathologies and life events influence both mental health and physiological problems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Regulatory Innate Lymphoid Cells Control Innate Intestinal Inflammation.

    Science.gov (United States)

    Wang, Shuo; Xia, Pengyan; Chen, Yi; Qu, Yuan; Xiong, Zhen; Ye, Buqing; Du, Ying; Tian, Yong; Yin, Zhinan; Xu, Zhiheng; Fan, Zusen

    2017-09-21

    An emerging family of innate lymphoid cells (termed ILCs) has an essential role in the initiation and regulation of inflammation. However, it is still unclear how ILCs are regulated in the duration of intestinal inflammation. Here, we identify a regulatory subpopulation of ILCs (called ILCregs) that exists in the gut and harbors a unique gene identity that is distinct from that of ILCs or regulatory T cells (Tregs). During inflammatory stimulation, ILCregs can be induced in the intestine and suppress the activation of ILC1s and ILC3s via secretion of IL-10, leading to protection against innate intestinal inflammation. Moreover, TGF-β1 is induced by ILCregs during the innate intestinal inflammation, and autocrine TGF-β1 sustains the maintenance and expansion of ILCregs. Therefore, ILCregs play an inhibitory role in the innate immune response, favoring the resolution of intestinal inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Treatment of orbital inflammation with rituximab in Wegener's granulomatosis

    DEFF Research Database (Denmark)

    Baslund, Bo; Wiencke, Anne Katrine; Rasmussen, Niels

    2012-01-01

    OBJECTIVES: To study the efficacy of rituximab therapy for the treatment of orbital inflammation in patients with Wegener's granulomatosis (WG). METHODS: Ten WG patients with orbital inflammation were included in this case-series. None had symptoms suggestive of extra-orbital disease activity...... inflammation. All patients were treated with 1000 mg of rituximab administered twice with an interval of 14 days between the infusions. Six months after therapy, a physical examination and a control computerised tomography (CT) scan was performed. RESULTS: All patients had orbital inflammation demonstrated...... the size of the orbital mass was unchanged in eight patients. CONCLUSIONS: Rituximab therapy has positive effects on symptoms, visual acuity and/or granuloma size in some WG patients with orbital inflammation. Treatment with rituximab should be considered in WG patients with this serious manifestation...

  10. Diabetes and the Brain: Oxidative Stress, Inflammation, and Autophagy

    Directory of Open Access Journals (Sweden)

    María Muriach

    2014-01-01

    Full Text Available Diabetes mellitus is a common metabolic disorder associated with chronic complications including a state of mild to moderate cognitive impairment, in particular psychomotor slowing and reduced mental flexibility, not attributable to other causes, and shares many symptoms that are best described as accelerated brain ageing. A common theory for aging and for the pathogenesis of this cerebral dysfunctioning in diabetes relates cell death to oxidative stress in strong association to inflammation, and in fact nuclear factor κB (NFκB, a master regulator of inflammation and also a sensor of oxidative stress, has a strategic position at the crossroad between oxidative stress and inflammation. Moreover, metabolic inflammation is, in turn, related to the induction of various intracellular stresses such as mitochondrial oxidative stress, endoplasmic reticulum (ER stress, and autophagy defect. In parallel, blockade of autophagy can relate to proinflammatory signaling via oxidative stress pathway and NFκB-mediated inflammation.

  11. Diabetes and the brain: oxidative stress, inflammation, and autophagy.

    Science.gov (United States)

    Muriach, María; Flores-Bellver, Miguel; Romero, Francisco J; Barcia, Jorge M

    2014-01-01

    Diabetes mellitus is a common metabolic disorder associated with chronic complications including a state of mild to moderate cognitive impairment, in particular psychomotor slowing and reduced mental flexibility, not attributable to other causes, and shares many symptoms that are best described as accelerated brain ageing. A common theory for aging and for the pathogenesis of this cerebral dysfunctioning in diabetes relates cell death to oxidative stress in strong association to inflammation, and in fact nuclear factor κB (NFκB), a master regulator of inflammation and also a sensor of oxidative stress, has a strategic position at the crossroad between oxidative stress and inflammation. Moreover, metabolic inflammation is, in turn, related to the induction of various intracellular stresses such as mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, and autophagy defect. In parallel, blockade of autophagy can relate to proinflammatory signaling via oxidative stress pathway and NFκB-mediated inflammation.

  12. The role of serratiopeptidase in the resolution of inflammation

    Directory of Open Access Journals (Sweden)

    Manju Tiwari

    2017-05-01

    Full Text Available Inflammation remains a key event during most of the diseases and physiological imbalance. Acute inflammation is an essential physiological event by immune system for a protective measure to remove cause of inflammation and failure of resolution lead to chronic inflammation. Over a period of time, a number of drugs mostly chemical have been deployed to combat acute and chronic inflammation. Recently, enzyme based anti-inflammatory drugs became popular over conventional chemical based drugs. Serratiopeptidase, a proteolytic enzyme from trypsin family, possesses tremendous scope in combating inflammation. Serine protease possesses a higher affinity for cyclooxygenase (COX-I and COX-II, a key enzyme associated with production of different inflammatory mediators including interleukins (IL, prostaglandins (PGs and thromboxane (TXs etc. Currently, arthritis, sinusitis, bronchitis, fibrocystic breast disease, and carpal tunnel syndrome, etc. are the leading inflammatory disorders that affected the entire the globe. In order to conquer inflammation, both acute and chronic world, physician mostly relies on conventional drugs. The most common drugs to combat acute inflammation are Nonsteroidal anti-inflammatory drugs (NSAIDs alone and or in combination with other drugs. However, during chronic inflammation, NSAIDs are often used with steroidal drugs such as autoimmune disorders. These drugs possess several limitations such as side effects, ADR, etc. In order to overcome these limitations and complications, enzyme based drugs (anti-inflammatory emerged, and aim for a new high since the last decade. Serine protease, the largest proteolytic family has been reported for several therapeutic applications, including anti-inflammatory. Serratiopeptidase is a leading enzyme which has a very long history in medical as an effective anti-inflammatory drug. Current study emphasizes present scenario and future prospect of serratiopeptidase as an anti-inflammatory drug

  13. Innate Lymphoid Cells in Intestinal Inflammation

    Science.gov (United States)

    Geremia, Alessandra; Arancibia-Cárcamo, Carolina V.

    2017-01-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine that encompasses Crohn’s disease (CD) and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC) in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses. ILC lack an antigen-specific receptor, but can respond to environmental stress signals contributing to the rapid orchestration of an early immune response. Several subsets of ILC reflecting functional characteristics of T helper subsets have been described. ILC1 express the transcription factor T-bet and are characterized by secretion of IFNγ, ILC2 are GATA3+ and secrete IL5 and IL13 and ILC3 depend on expression of RORγt and secrete IL17 and IL22. However, ILC retain a degree of plasticity depending on exposure to cytokines and environmental factors. IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF. We have previously identified IL23 responsive ILC in the human intestine and found that they accumulate in the inflamed colon and small bowel of patients with CD. Other studies have confirmed accumulation of ILC in CD with increased frequencies of IFNγ-secreting ILC1 in both the intestinal lamina propria and the epithelium. Moreover, IL23 driven IL22 producing ILC have been shown to drive bacteria-induced colitis-associated cancer in mice. Interestingly, our data show increased ILC accumulation in patients with IBD and primary sclerosing cholangitis, who carry an increased risk of

  14. Innate Lymphoid Cells in Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Alessandra Geremia

    2017-10-01

    Full Text Available Inflammatory bowel disease (IBD is a chronic inflammatory disorder of the intestine that encompasses Crohn’s disease (CD and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses. ILC lack an antigen-specific receptor, but can respond to environmental stress signals contributing to the rapid orchestration of an early immune response. Several subsets of ILC reflecting functional characteristics of T helper subsets have been described. ILC1 express the transcription factor T-bet and are characterized by secretion of IFNγ, ILC2 are GATA3+ and secrete IL5 and IL13 and ILC3 depend on expression of RORγt and secrete IL17 and IL22. However, ILC retain a degree of plasticity depending on exposure to cytokines and environmental factors. IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF. We have previously identified IL23 responsive ILC in the human intestine and found that they accumulate in the inflamed colon and small bowel of patients with CD. Other studies have confirmed accumulation of ILC in CD with increased frequencies of IFNγ-secreting ILC1 in both the intestinal lamina propria and the epithelium. Moreover, IL23 driven IL22 producing ILC have been shown to drive bacteria-induced colitis-associated cancer in mice. Interestingly, our data show increased ILC accumulation in patients with IBD and primary sclerosing cholangitis, who carry an

  15. Synovial tissue hypoxia and inflammation in vivo.

    LENUS (Irish Health Repository)

    Ng, C T

    2012-02-01

    INTRODUCTION: Hypoxia is a microenvironmental feature in the inflamed joint, which promotes survival advantage for cells. The aim of this study was to examine the relationship of partial oxygen pressure in the synovial tissue (tPO(2)) in patients with inflammatory arthritis with macroscopic\\/microscopic inflammation and local levels of proinflammatory mediators. METHODS: Patients with inflammatory arthritis underwent full clinical assessment and video arthroscopy to quantify macroscopic synovitis and measure synovial tPO(2) under direct visualisation. Cell specific markers (CD3 (T cells), CD68 (macrophages), Ki67 (cell proliferation) and terminal deoxynucleotidyl transferase dUTP nick end labelling (cell apoptosis)) were quantified by immunohistology. In vitro migration was assessed in primary and normal synoviocytes (synovial fibroblast cells (SFCs)) using a wound repair scratch assay. Levels of tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), interferon gamma (IFNgamma), IL6, macrophage inflammatory protein 3alpha (MIP3alpha) and IL8 were quantified, in matched serum and synovial fluid, by multiplex cytokine assay and ELISA. RESULTS: The tPO(2) was 22.5 (range 3.2-54.1) mm Hg and correlated inversely with macroscopic synovitis (r=-0.421, p=0.02), sublining CD3 cells (-0.611, p<0.01) and sublining CD68 cells (r=-0.615, p<0.001). No relationship with cell proliferation or apoptosis was found. Primary and normal SFCs exposed to 1% and 3% oxygen (reflecting the median tPO(2) in vivo) induced cell migration. This was coupled with significantly higher levels of synovial fluid tumour necrosis factor alpha (TNFalpha), IL1beta, IFNgamma and MIP3alpha in patients with tPO(2) <20 mm Hg (all p values <0.05). CONCLUSIONS: This is the first study to show a direct in vivo correlation between synovial tPO(2), inflammation and cell migration, thus it is proposed that hypoxia is a possible primary driver of inflammatory processes in the arthritic joint.

  16. Meconium aspiration syndrome: a role for fetal systemic inflammation.

    Science.gov (United States)

    Lee, JoonHo; Romero, Roberto; Lee, Kyung A; Kim, Eun Na; Korzeniewski, Steven J; Chaemsaithong, Piya; Yoon, Bo Hyun

    2016-03-01

    Meconium aspiration syndrome (MAS) is a leading cause of morbidity and mortality in term infants. Meconium-stained amniotic fluid (MSAF) occurs in approximately 1 of every 7 pregnancies, but only 5% of neonates exposed to MSAF develop MAS. Why some infants exposed to meconium develop MAS while others do not is a fundamental question. Patients with MSAF have a higher frequency of intraamniotic inflammation/infection than those with clear fluid. We propose that fetal systemic inflammation is a risk factor for the development of MAS in patients with MSAF. We sought to investigate whether intraamniotic inflammation and funisitis, the histopathologic landmark of a fetal inflammatory response, predispose to MAS. A prospective cohort study was conducted from 1995 through 2009. Amniotic fluid (AF) samples (n = 1281) were collected at the time of cesarean delivery from women who delivered singleton newborns at term (gestational age ≥38 weeks). Intraamniotic inflammation was diagnosed if the AF concentration of matrix metalloproteinase-8 was >23 ng/mL. Funisitis was diagnosed by histologic examination if inflammation was present in the umbilical cord. The prevalence of MSAF was 9.2% (118/1281), and 10.2% (12/118) of neonates exposed to MSAF developed MAS. There were no significant differences in the median gestational age or umbilical cord arterial pH at birth between neonates who developed MAS and those who did not (each P > .1). Mothers whose newborns developed MAS had a higher median of AF matrix metalloproteinase-8 (456.8 vs 157.2 ng/mL, P inflammation had a higher rate of MAS than those who were not exposed to intraamniotic inflammation [13.0% (10/77) vs 0% (0/32), P = .03], as did those exposed to funisitis [31.3% (5/16) vs 7.3% (6/82); relative risk, 4.3; 95% confidence interval, 1.5-12.3]. Among the 89 newborns for whom both AF and placental histology were available, MAS was more common in patients with both intraamniotic inflammation and funisitis than in those

  17. DMPD: Pathways connecting inflammation and cancer. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18325755 Pathways connecting inflammation and cancer. Allavena P, Garlanda C, Borre...) (.csml) Show Pathways connecting inflammation and cancer. PubmedID 18325755 Title Pathways connecting inflammation

  18. NOD2 and inflammation: current insights

    Directory of Open Access Journals (Sweden)

    Negroni A

    2018-02-01

    Full Text Available Anna Negroni,1 Maria Pierdomenico,2 Salvatore Cucchiara,2 Laura Stronati3 1Division of Health Protection Technologies, Territorial and Production Systems Sustainability Department, ENEA, Rome, Italy; 2Department of Pediatrics and Infantile Neuropsychiatry, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy; 3Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy Abstract: The nucleotide-binding oligomerization domain (NOD protein, NOD2, belonging to the intracellular NOD-like receptor family, detects conserved motifs in bacterial peptidoglycan and promotes their clearance through activation of a proinflammatory transcriptional program and other innate immune pathways, including autophagy and endoplasmic reticulum stress. An inactive form due to mutations or a constitutive high expression of NOD2 is associated with several inflammatory diseases, suggesting that balanced NOD2 signaling is critical for the maintenance of immune homeostasis. In this review, we discuss recent developments about the pathway and mechanisms of regulation of NOD2 and illustrate the principal functions of the gene, with particular emphasis on its central role in maintaining the equilibrium between intestinal microbiota and host immune responses to control inflammation. Furthermore, we survey recent studies illustrating the role of NOD2 in several inflammatory diseases, in particular, inflammatory bowel disease, of which it is the main susceptibility gene. Keywords: innate immunity, intestinal homeostasis, ER stress, autophagy, inflammatory bowel disease, extraintestinal disease

  19. Inflammation and internalizing disorders in adolescents.

    Science.gov (United States)

    Belem da Silva, Cristiano Tschiedel; de Abreu Costa, Marianna; Kapczinski, Flávio; de Aguiar, Bianca Wollenhaupt; Salum, Giovanni Abrahão; Manfro, Gisele Gus

    2017-07-03

    Serum inflammatory markers have been studied in adults with anxiety and depression, but little is known about cytokine levels in young adolescents with emotional disorders. The objective of this study is to compare serum levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) between adolescents with internalizing disorders and adolescents from the same community without internalizing disorders. A total of 134 non-medicated subjects (n=76 with internalizing disorders) were recruited from a larger sample of 2457 individuals. Serum levels of IL-6 and IL-10 were quantified and psychiatric diagnosis was evaluated using structured clinical interviews. Adolescents with internalizing disorders presented significantly higher levels of IL-6 as compared to youngsters without internalizing disorders. Differences between groups in IL-10 levels were not statistically significant. This study points out that IL-6 levels may be associated with internalizing disorders in youths and suggests that inflammation might be an early biomarker of emotional distress. High levels of cytokines may adversely affect general health in the long-term, which raise broader issues in terms of public health if results are replicated. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Myocardial Inflammation-Are We There Yet?

    Science.gov (United States)

    Greulich, Simon; Ferreira, Vanessa M; Dall'Armellina, Erica; Mahrholdt, Heiko

    Several exogenous or endogenous factors can lead to inflammatory heart disease. Beside infectious myocarditis, other systemic inflammatory disorders such as sarcoidosis, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Churg-Strauss syndrome, and rheumatoid arthritis can affect the myocardium. Myocardial inflammation may have a major impact on the outcome of these patients, resulting in sudden cardiac death, severe arrhythmias, or end-stage heart failure. The current gold standard for definite confirmation of inflammatory heart disease is endomyocardial biopsy (EMB), but is invasive and suffers low sensitivity and specificity due to sampling errors. Thus, non-invasive methods for detecting the extent and changes over time of the inflammatory myocardial disease are needed. Cardiac magnetic resonance (CMR) is such a non-invasive method. We will describe and discuss different approaches for CMR assessment of inflammatory myocardial disease including early gadolinium enhancement (EGE), T2-weighted imaging, late gadolinium enhancement (LGE), the newer mapping proton relaxation techniques (T1 pre-contrast, T1 post-contrast, T2 mapping), and the hybrid PET/MRI technique.

  1. Understanding about the classification of pulp inflammation

    Directory of Open Access Journals (Sweden)

    Trijoedani Widodo

    2007-03-01

    Full Text Available Since most authors use the reversible pulpitis and irreversible pulpitis classification, however, many dentists still do not implement these new classifications. Research was made using a descriptive method by proposing questionnaire to dentists from various dental clinics. The numbers of the dentists participating in this research are 22 dentists. All respondents use the diagnosis sheet during their examinations on patients. Nonetheless, it can't be known what diagnosis card used and most of the dentists are still using the old classification. Concerning responses given towards the new classification: a the new classification had been heard, however, it was not clear (36.3%; b the new classification has never been heard at all (63.6%. Then, responses concerning whether a new development is important to be followed-up or not: a there are those who think that information concerning new development is very important (27.2%; b those who feel that it is important to have new information (68.3%; c those who think that new information is not important (8%. It concluded that information concerning the development of classification of pulp inflammation did not reach the dentists.

  2. Modeling and Hemofiltration Treatment of Acute Inflammation

    Directory of Open Access Journals (Sweden)

    Robert S. Parker

    2016-10-01

    Full Text Available The body responds to endotoxins by triggering the acute inflammatory response system to eliminate the threat posed by gram-negative bacteria (endotoxin and restore health. However, an uncontrolled inflammatory response can lead to tissue damage, organ failure, and ultimately death; this is clinically known as sepsis. Mathematical models of acute inflammatory disease have the potential to guide treatment decisions in critically ill patients. In this work, an 8-state (8-D differential equation model of the acute inflammatory response system to endotoxin challenge was developed. Endotoxin challenges at 3 and 12 mg/kg were administered to rats, and dynamic cytokine data for interleukin (IL-6, tumor necrosis factor (TNF, and IL-10 were obtained and used to calibrate the model. Evaluation of competing model structures was performed by analyzing model predictions at 3, 6, and 12 mg/kg endotoxin challenges with respect to experimental data from rats. Subsequently, a model predictive control (MPC algorithm was synthesized to control a hemoadsorption (HA device, a blood purification treatment for acute inflammation. A particle filter (PF algorithm was implemented to estimate the full state vector of the endotoxemic rat based on time series cytokine measurements. Treatment simulations show that: (i the apparent primary mechanism of HA efficacy is white blood cell (WBC capture, with cytokine capture a secondary benefit; and (ii differential filtering of cytokines and WBC does not provide substantial improvement in treatment outcomes vs. existing HA devices.

  3. Inorganic polyphosphate: a key modulator of inflammation.

    Science.gov (United States)

    Hassanian, S M; Avan, A; Ardeshirylajimi, A

    2017-02-01

    Inorganic polyphosphate (PolyP) is a molecule with prothrombotic and proinflammatory properties in blood. PolyP activates the NF-κB signaling pathway, increases the expression of cell surface adhesion molecules and disrupts the vascular barrier integrity of endothelial cells. PolyP-induced NF-κB activation and vascular hyperpermeability are regulated by the mammalian target of rapamycin complex-1 (mTORC1) and mTORC2 pathways, respectively. Through interaction with receptor for advanced glycation end products (RAGE) and P2Y1 receptors, PolyP dramatically amplifies the proinflammatory responses of nuclear proteins. Moreover, PolyP-mediated activation of the contact pathway results in activation of the kallikrein-kinin system, which either directly or in cross-talk with the complement system induces inflammation in both cellular and animal systems. Thus, polyP is a novel therapeutic target for the treatment of metabolic and acute/chronic proinflammatory diseases, including severe sepsis, diabetes, cardiovascular disease and cancer. In this review, we discuss recent findings on the inflammatory properties of polyP and propose a model to explain the molecular mechanism of proinflammatory effects of this molecule in different systems. © 2016 International Society on Thrombosis and Haemostasis.

  4. Inflammation Thread Runs across Medical Laboratory Specialities

    Directory of Open Access Journals (Sweden)

    Urs Nydegger

    2016-01-01

    Full Text Available We work on the assumption that four major specialities or sectors of medical laboratory assays, comprising clinical chemistry, haematology, immunology, and microbiology, embraced by genome sequencing techniques, are routinely in use. Medical laboratory markers for inflammation serve as model: they are allotted to most fields of medical lab assays including genomics. Incessant coding of assays aligns each of them in the long lists of big data. As exemplified with the complement gene family, containing C2, C3, C8A, C8B, CFH, CFI, and ITGB2, heritability patterns/risk factors associated with diseases with genetic glitch of complement components are unfolding. The C4 component serum levels depend on sufficient vitamin D whilst low vitamin D is inversely related to IgG1, IgA, and C3 linking vitamin sufficiency to innate immunity. Whole genome sequencing of microbial organisms may distinguish virulent from nonvirulent and antibiotic resistant from nonresistant varieties of the same species and thus can be listed in personal big data banks including microbiological pathology; the big data warehouse continues to grow.

  5. IL-12 protects from psoriasiform skin inflammation.

    Science.gov (United States)

    Kulig, Paulina; Musiol, Stephanie; Freiberger, Sandra Nicole; Schreiner, Bettina; Gyülveszi, Gabor; Russo, Giancarlo; Pantelyushin, Stanislav; Kishihara, Kenji; Alessandrini, Francesca; Kündig, Thomas; Sallusto, Federica; Hofbauer, Günther F L; Haak, Stefan; Becher, Burkhard

    2016-11-28

    Neutralization of the common p40-subunit of IL-12/23 in psoriasis patients has led to a breakthrough in the management of moderate to severe disease. Aside from neutralizing IL-23, which is thought to be responsible for the curative effect, anti-p40 therapy also interferes with IL-12 signalling and type 1 immunity. Here we dissect the individual contribution of these two cytokines to the formation of psoriatic lesions and understand the effect of therapeutic co-targeting of IL-12 and IL-23 in psoriasis. Using a preclinical model for psoriatic plaque formation we show that IL-12, in contrast to IL-23, has a regulatory function by restraining the invasion of an IL-17-committed γδT (γδT17) cell subset. We discover that IL-12 receptor signalling in keratinocytes initiates a protective transcriptional programme that limits skin inflammation, suggesting that collateral targeting of IL-12 by anti-p40 monoclonal antibodies is counterproductive in the therapy of psoriasis.

  6. Sleep, immunity and inflammation in gastrointestinal disorders.

    Science.gov (United States)

    Ali, Tauseef; Choe, James; Awab, Ahmed; Wagener, Theodore L; Orr, William C

    2013-12-28

    Sleep disorders have become a global issue, and discovering their causes and consequences are the focus of many research endeavors. An estimated 70 million Americans suffer from some form of sleep disorder. Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability, slower response times and performance detriments. Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health, economic consequences, and most importantly increased all-cause mortality. Several research studies support the associations among sleep, immune function and inflammation. Here, we review the current research linking sleep, immune function, and gastrointestinal diseases and discuss the interdependent relationship between sleep and these gastrointestinal disorders. Different physiologic processes including immune system and inflammatory cytokines help regulate the sleep. The inflammatory cytokines such as tumor necrosis factor, interleukin-1 (IL-1), and IL-6 have been shown to be a significant contributor of sleep disturbances. On the other hand, sleep disturbances such as sleep deprivation have been shown to up regulate these inflammatory cytokines. Alterations in these cytokine levels have been demonstrated in certain gastrointestinal diseases such as inflammatory bowel disease, gastro-esophageal reflux, liver disorders and colorectal cancer. In turn, abnormal sleep brought on by these diseases is shown to contribute to the severity of these same gastrointestinal diseases. Knowledge of these relationships will allow gastroenterologists a great opportunity to enhance the care of their patients.

  7. The blood-epididymis barrier and inflammation

    Science.gov (United States)

    Gregory, Mary; Cyr, Daniel G

    2014-01-01

    The blood-epididymis barrier (BEB) is a critical structure for male fertility. It enables the development of a specific luminal environment that allows spermatozoa to acquire both the ability to swim and fertilize an ovum. The presence of tight junctions and specific cellular transporters can regulate the composition of the epididymal lumen to favor proper sperm maturation. The BEB is also at the interface between the immune system and sperm. Not only does the BEB protect maturing spermatozoa from the immune system, it is also influenced by cytokines released during inflammation, which can result in the loss of barrier function. Such a loss is associated with an immune response, decreased sperm functions, and appears to be a contributing factor to post-testicular male infertility. Alterations in the BEB may be responsible for the formation of inflammatory conditions such as sperm granulomas. The present review summarizes current knowledge on the morphological, physiological and pathological components associated with the BEB, the role of immune function on the regulation of the BEB, and how disturbance of these factors can result in inflammatory lesions of the epididymis. PMID:26413391

  8. Wogonin Induces Eosinophil Apoptosis and Attenuates Allergic Airway Inflammation

    Science.gov (United States)

    Dorward, David A.; Sharma, Sidharth; Rennie, Jillian; Felton, Jennifer M.; Alessandri, Ana L.; Duffin, Rodger; Schwarze, Jurgen; Haslett, Christopher; Rossi, Adriano G.

    2015-01-01

    Rationale: Eosinophils are key effector cells in allergic diseases, including allergic rhinitis, eczema, and asthma. Their tissue presence is regulated by both recruitment and increased longevity at inflamed sites. Objectives: To investigate the ability of the flavone wogonin to induce eosinophil apoptosis in vitro and attenuate eosinophil-dominant allergic inflammation in vivo in mice. Methods: Human and mouse eosinophil apoptosis in response to wogonin was investigated by cellular morphology, flow cytometry, mitochondrial membrane permeability, and pharmacological caspase inhibition. Allergic lung inflammation was modeled in mice sensitized and challenged with ovalbumin. Bronchoalveolar lavage (BAL) and lung tissue were examined for inflammation, mucus production, and inflammatory mediator production. Airway hyperresponsiveness to aerosolized methacholine was measured. Measurements and Main Results: Wogonin induced time- and concentration-dependent human and mouse eosinophil apoptosis in vitro. Wogonin-induced eosinophil apoptosis occurred with activation of caspase-3 and was inhibited by pharmacological caspase inhibition. Wogonin administration attenuated allergic airway inflammation in vivo with reductions in BAL and interstitial eosinophil numbers, increased eosinophil apoptosis, reduced airway mucus production, and attenuated airway hyperresponsiveness. This wogonin-induced reduction in allergic airway inflammation was prevented by concurrent caspase inhibition in vivo. Conclusions: Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation, suggesting that it has therapeutic potential for the treatment of allergic inflammation in humans. PMID:25629436

  9. Effects of inflammation on stem cells: together they strive?

    Science.gov (United States)

    Kizil, Caghan; Kyritsis, Nikos; Brand, Michael

    2015-01-01

    Inflammation entails a complex set of defense mechanisms acting in concert to restore the homeostatic balance in organisms after damage or pathogen invasion. This immune response consists of the activity of various immune cells in a highly complex manner. Inflammation is a double-edged sword as it is reported to have both detrimental and beneficial consequences. In this review, we discuss the effects of inflammation on stem cell activity, focusing primarily on neural stem/progenitor cells in mammals and zebrafish. We also give a brief overview of the effects of inflammation on other stem cell compartments, exemplifying the positive and negative role of inflammation on stemness. The majority of the chronic diseases involve an unremitting phase of inflammation due to improper resolution of the initial pro-inflammatory response that impinges on the stem cell behavior. Thus, understanding the mechanisms of crosstalk between the inflammatory milieu and tissue-resident stem cells is an important basis for clinical efforts. Not only is it important to understand the effect of inflammation on stem cell activity for further defining the etiology of the diseases, but also better mechanistic understanding is essential to design regenerative therapies that aim at micromanipulating the inflammatory milieu to offset the negative effects and maximize the beneficial outcomes. PMID:25739812

  10. Inflammation and pharmacokinetics: potential implications for HIV-infection.

    Science.gov (United States)

    Seifert, Sharon M; Castillo-Mancilla, Jose R; Erlandson, Kristine M; Anderson, Peter L

    2017-06-01

    The physiological changes accompanying inflammation may alter the pharmacokinetics (PK) of certain medications. Individuals infected with HIV have chronically elevated inflammatory markers despite viral suppression following effective antiretroviral therapy (ART), as well as age-related inflammation. Understanding the potential clinical implications of inflammation on the PK of medications is important for understanding dose-response relationships and necessitates future research. Areas covered: An extensive literature search was carried out using PubMed and associated bibliographies to summarize the current state of knowledge regarding altered PK in response to inflammation and its application to the field of HIV. Expert opinion: Preclinical and clinical studies show that inflammation leads to a downregulation of certain drug metabolizing enzymes and both up and down regulation of transporters depending on the transporter and cell type. Decreased gastric acidity, fluid shifts, and plasma protein alterations also occur with inflammation, leading to potential absorption, distribution, and clearance changes. More research is needed including controlled PK studies to address the clinical relevance of these observations, especially in the aging HIV-infected population. Results from future studies will enable us to better predict drug concentrations in individuals with inflammation, in line with efforts to provide personalized pharmacotherapy in our healthcare system.

  11. Prostatic inflammation induces urinary frequency in adult mice.

    Directory of Open Access Journals (Sweden)

    Sanghee Lee

    Full Text Available Lower urinary tract symptoms (LUTS including urinary frequency and nocturia are common in aging men. Recent studies have revealed a strong association of prostatic inflammation with LUTS. We developed an animal model of bacterial induced, isolated prostatic inflammation and examined the effect of prostatic inflammation on voiding behavior in adult C57BL/6J mice. Prostatic inflammation was induced by transurethral inoculation of uropathogenic E. coli-1677. Bacterial cystitis was prevented by continuous administration of nitrofurantoin. Hematoxylin and eosin (H&E staining and bacterial culture were preformed to validate our animal model. Voiding behavior was examined by metabolic cage testing on post-instillation day 1 (PID 1, PID 4, PID 7 and PID 14 and both voiding frequency and volume per void were determined. Mice with prostatic inflammation showed significantly increased voiding frequency at PID 1, 7 and 14, and decreased volume per void at all time points, as compared to mice instilled with saline and receiving nitrofurantoin (NTF. Linked analysis of voiding frequency and voided volumes revealed an overwhelming preponderance of high frequency, low volume voiding in mice with prostatic inflammation. These observations suggest that prostatic inflammation may be causal for symptoms of urinary frequency and nocturia.

  12. Activation and resolution of periodontal inflammation and its systemic impact.

    Science.gov (United States)

    Hasturk, Hatice; Kantarci, Alpdogan

    2015-10-01

    Inflammation is a highly organized event impacting upon organs, tissues and biological systems. Periodontal diseases are characterized by dysregulation or dysfunction of resolution pathways of inflammation that results in failure to heal and in a dominant chronic, progressive, destructive and predominantly unresolved inflammation. The biological consequences of inflammatory processes may be independent of the etiological agents, such as trauma, microbial organisms and stress. The impact of the inflammatory pathological process depends upon the tissues or organ system affected. Whilst mediators are similar, there is tissue specificity for the inflammatory events. It is plausible that inflammatory processes in one organ could directly lead to pathologies in another organ or tissue. Communication between distant parts of the body and their inflammatory status is also mediated by common signaling mechanisms mediated via cells and soluble mediators. This review focuses on periodontal inflammation, its systemic associations and advances in therapeutic approaches based on mediators acting through orchestration of natural pathways to resolution of inflammation. We also discuss a new treatment concept in which natural pathways of resolution of periodontal inflammation can be used to limit systemic inflammation and promote healing and regeneration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. [Role of inflammation in the etiopathogenesis of COPD].

    Science.gov (United States)

    del Puerto-Nevado, Laura; Pérez-Rial, Sandra; Girón-Martínez, Alvaro; Peces-Barba, Germán

    2010-12-01

    Inflammation is one of the first immune system responses to any type of aggression. As with any type of aggression, the lesion produced by inhalation of tobacco smoke prompts an innate inflammatory response. Subsequently, this lesion is stimulated by the release of various chemical factors that enhance the inflammatory response and, finally--depending on the type of aggression--acquired immunity is activated, which, mediated by lymphocyte participation, serves to establish a physical barrier against the propagation of the lesion and to aid repair of the damaged pulmonary tissue. However, the balance between inflammation and repair is not always maintained, as is the case in chronic obstructive pulmonary disease (COPD), in which marked changes appear in the architecture of the airways, alveolar spaces and pulmonary arteries, forming the structural background of the functional changes characteristic of this disease. COPD is basically a pulmonary disease but data are available on the existence of associated systemic inflammation. The origins of this systemic inflammation are unclear: some information indicates that tobacco smoke is a direct origin common to local and systemic inflammation, while other data point to primary pulmonary inflammation that secondarily produces systemic involvement. The present review describes the main mechanisms involved in both pulmonary and systemic inflammation in COPD. Copyright © 2010 Sociedad Española de Neumología y Cirugía Torácica. Published by Elsevier Espana. All rights reserved.

  14. Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation.

    Science.gov (United States)

    Iyengar, Neil M; Gucalp, Ayca; Dannenberg, Andrew J; Hudis, Clifford A

    2016-12-10

    Purpose There is growing evidence that inflammation is a central and reversible mechanism through which obesity promotes cancer risk and progression. Methods We review recent findings regarding obesity-associated alterations in the microenvironment and the local and systemic mechanisms through which these changes support tumor growth. Results Locally, hyperadiposity is associated with altered adipose tissue function, adipocyte death, and chronic low-grade inflammation. Most individuals who are obese harbor inflamed adipose tissue, which resembles chronically injured tissue, with immune cell infiltration and remodeling. Within this distinctly altered local environment, several pathophysiologic changes are found that may promote breast and other cancers. Consistently, adipose tissue inflammation is associated with a worse prognosis in patients with breast and tongue cancers. Systemically, the metabolic syndrome, including dyslipidemia and insulin resistance, occurs in the setting of adipose inflammation and operates in concert with local mechanisms to sustain the inflamed microenvironment and promote tumor growth. Importantly, adipose inflammation and its protumor consequences can be found in some individuals who are not considered to be obese or overweight by body mass index. Conclusion The tumor-promoting effects of obesity occur at the local level via adipose inflammation and associated alterations in the microenvironment, as well as systemically via circulating metabolic and inflammatory mediators associated with adipose inflammation. Accurately characterizing the obese state and identifying patients at increased risk for cancer development and progression will likely require more precise assessments than body mass index alone. Biomarkers of adipose tissue inflammation would help to identify high-risk populations. Moreover, adipose inflammation is a reversible process and represents a novel therapeutic target that warrants further study to break the obesity

  15. Bronchial inflammation and hyperresponsiveness in well controlled asthma.

    Science.gov (United States)

    Muñoz, X; Sanchez-Vidaurre, S; Roca, O; Torres, F; Morell, F; Cruz, M J

    2012-09-01

    Little research has been devoted to the characteristics of bronchial inflammation in patients with stable, well controlled asthma. The aim of this study was to assess the degree and type of airway inflammation and to investigate the relationship between inflammation and bronchial hyperresponsiveness in patients with well controlled asthma. A cross-sectional study was conducted in 84 adult patients (43 men, mean age 43 years) with documented well controlled asthma. Induced sputum samples were obtained and cell types determined by differential cell count. Spirometry and methacholine challenge testing were performed. Asthma Control Questionnaire (ACQ) was used to assess symptoms. Patients were included if their ACQ score was bronchial inflammation: 28 cases were considered eosinophilic, 28 neutrophilic, and 3 mixed. Median (range) percentage of eosinophils was 4% (0-64) in patients testing positive to methacholine challenge (n = 66) and 1% (0-3) in those testing negative (n = 18) (P = 0.003). A positive correlation was found between eosinophil percentage and the methacholine dose/response ratio (r = 0.477, P = 0.0001). The geometric mean (95% CI) of the methacholine PC20 was 1.74 mg/mL (1.04-2.93) in patients with eosinophilic inflammation and 4.14 mg/mL (2.5-6.84) in those with neutrophilic inflammation (P = 0.03). Inflammation and bronchial hyperresponsiveness persist in most patients with well controlled asthma. The study demonstrates that eosinophilic or neutrophilic inflammation persisted in most well controlled asthma patients despite the fact that their condition was controlled and therefore, measurement of bronchial inflammation seems essential to achieve proper asthma control. © 2012 Blackwell Publishing Ltd.

  16. Neuro-inflammation, blood-brain barrier, seizures and autism

    Directory of Open Access Journals (Sweden)

    Theoharides Theoharis C

    2011-11-01

    Full Text Available Abstract Many children with Autism Spectrum Diseases (ASD present with seizure activity, but the pathogenesis is not understood. Recent evidence indicates that neuro-inflammation could contribute to seizures. We hypothesize that brain mast cell activation due to allergic, environmental and/or stress triggers could lead to focal disruption of the blood-brain barrier and neuro-inflammation, thus contributing to the development of seizures. Treating neuro-inflammation may be useful when anti-seizure medications are ineffective.

  17. Persistent low-grade inflammation and regular exercise

    DEFF Research Database (Denmark)

    Åström, Maj-brit; Feigh, Michael; Pedersen, Bente Klarlund

    2010-01-01

    Persistent low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes and dementia and evidence exists that inflammation is a causal factor in the development of insulin resistance and atherosclerosis. Regular exercise offers protection...... against all of these diseases and recent evidence suggests that the protective effect of exercise may to some extent be ascribed to an anti-inflammatory effect of regular exercise. Visceral adiposity contributes to systemic inflammation and is independently associated with the occurrence of CVD, type 2...

  18. A case of relapsing flitting bilateral idiopathic orbital inflammation.

    LENUS (Irish Health Repository)

    Browne, Michelle Ann

    2009-12-01

    Idiopathic orbital inflammation (IOI) is defined as a benign non-infective clinical syndrome characterized by features of non-specific inflammation of the orbit without identifiable local or systemic causes. This can be called orbital myositis if the inflammation is predominantly in the orbital muscles. It is a diagnosis of exclusion based on clinical, radiological, and if necessary, histological findings. The most commons symptoms are swelling, ptosis, proptosis and painful eye movements. To our knowledge, this patient is the first with IOI to demonstrate relapsing flitting bilateral involvement of several individual extra-ocular muscles.

  19. Chemokines and chemokine receptors in inflammation of the nervous system

    DEFF Research Database (Denmark)

    Huang, D; Han, Yong-Chang; Rani, M R

    2000-01-01

    This article focuses on the production of chemokines by resident glial cells of the nervous system. We describe studies in two distinct categories of inflammation within the nervous system: immune-mediated inflammation as seen in experimental autoimmune encephalomyelitis (EAE) or multiple sclerosis...... (MS) and post-traumatic inflammation. We provide evidence that chemokines play a role in amplifying the inflammatory reaction in EAE (and, probably, MS). In the context of neural trauma, chemokines appear to be primary stimuli for leukocyte recruitment. Strikingly, expression of monocyte...

  20. Menopause, obesity and inflammation: interactive risk factors for Alzheimer's disease.

    Science.gov (United States)

    Christensen, Amy; Pike, Christian J

    2015-01-01

    Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder, the development of which is regulated by several environmental and genetic risk factors. Two factors theorized to contribute to the initiation and/or progression of AD pathogenesis are age-related increases in inflammation and obesity. These factors may be particularly problematic in women. The onset of menopause in mid-life elevates the vulnerability of women to AD, an increased risk that is likely associated with the depletion of estrogens. Menopause is also linked with an abundance of additional changes, including increased central adiposity and inflammation. Here, we review the current literature to explore the interactions between obesity, inflammation, menopause and AD.

  1. Inflammation and nutritional status assessment by malnutrition inflammation score and its outcome in pre-dialysis chronic kidney disease patients.

    Science.gov (United States)

    Jagadeswaran, D; Indhumathi, E; Hemamalini, A J; Sivakumar, V; Soundararajan, P; Jayakumar, M

    2018-01-09

    Malnutrition-inflammation complex syndrome (MICS), hyperhomocysteinemia, calcium and phosphate levels derangement have been predicted as important contributing factors for the progression of cardiovascular burden. Among patients with earlier stage of CKD, hypoalbuminaemia and inflammation deliberated as non-traditional cardiovascular risk factors, which add more burden to circulatory disease, mortality and rapid advancement to CKD stage 5. The aim of the study is to evaluate inflammation and nutritional status of CKD patients not on dialysis using Malnutrition inflammation score (MIS) and to verify the association with mortality in the follow-up period. In this prospective cohort study 129 (66 males, 63 females) pre-dialysis CKD patients enrolled between June 2013 to August 2014 and censored until March 2017. Malnutrition and Inflammation assessed using Malnutrition inflammation score. Blood urea nitrogen, serum creatinine, albumin, Interleukin - 6, highly sensitive C reactive protein (hsCRP), total cholesterol and anthropometric data were analyzed. The Malnutrition inflammation score in pre-dialysis CKD patients ranged from 0 to 18 with the median score of two. During 36 or more months of follow-up, there were 30 (23.2%) deaths, 35 (27%) patients initiated on hemodialysis, one (0.7%) patient was initiated on peritoneal dialysis, two (1.4%) patients underwent renal transplantation and two (1.4%) patients were lost for follow-up. In this study, 33% had varying degree of malnutrition and inflammation. Patients who had MIS ≥7 had significant increase in IL-6 (p = 0.003) and HsCRP levels (p nutritional status and inflammation using MIS regularly to prevent malnutrition and its associated complications through appropriate medical and nutritional intervention. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  2. Adjusting retinol-binding protein concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

    Science.gov (United States)

    Larson, Leila M; Namaste, Sorrel Ml; Williams, Anne M; Engle-Stone, Reina; Addo, O Yaw; Suchdev, Parminder S; Wirth, James P; Temple, Victor; Serdula, Mary; Northrop-Clewes, Christine A

    2017-07-01

    Background: The accurate estimation of the prevalence of vitamin A deficiency (VAD) is important in planning and implementing interventions. Retinol-binding protein (RBP) is often used in population surveys to measure vitamin A status, but its interpretation is challenging in settings where inflammation is common because RBP concentrations decrease during the acute-phase response. Objectives: We aimed to assess the relation between RBP concentrations and inflammation and malaria in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y) and to investigate adjustment algorithms to account for these effects. Design: Cross-sectional data from 8 surveys for PSC ( n = 8803) and 4 surveys for WRA ( n = 4191) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and combined with the use of a meta-analysis. Several approaches were explored to adjust RBP concentrations in PSC in inflammation and malaria settings as follows: 1 ) the exclusion of subjects with C-reactive protein (CRP) concentrations >5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L, 2 ) the application of arithmetic correction factors, and 3 ) the use of a regression correction approach. The impact of adjustment on the estimated prevalence of VAD (defined as inflammation. Depending on the approach used to adjust for inflammation (CRP+AGP), the estimated prevalence of VAD decreased by a median of 11-18 percentage points in PSC compared with unadjusted values. There was no added effect of adjusting for malaria on the estimated VAD after adjusting for CRP and AGP. Conclusions: The use of regression correction (derived from internal data), which accounts for the severity of inflammation, to estimate the prevalence of VAD in PSC in regions with inflammation and malaria is supported by the analysis of the BRINDA data. These findings contribute to the evidence on adjusting for

  3. Adjusting retinol-binding protein concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

    Science.gov (United States)

    Temple, Victor; Serdula, Mary; Northrop-Clewes, Christine A

    2017-01-01

    Background: The accurate estimation of the prevalence of vitamin A deficiency (VAD) is important in planning and implementing interventions. Retinol-binding protein (RBP) is often used in population surveys to measure vitamin A status, but its interpretation is challenging in settings where inflammation is common because RBP concentrations decrease during the acute-phase response. Objectives: We aimed to assess the relation between RBP concentrations and inflammation and malaria in preschool children (PSC) (age range: 6–59 mo) and women of reproductive age (WRA) (age range: 15–49 y) and to investigate adjustment algorithms to account for these effects. Design: Cross-sectional data from 8 surveys for PSC (n = 8803) and 4 surveys for WRA (n = 4191) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and combined with the use of a meta-analysis. Several approaches were explored to adjust RBP concentrations in PSC in inflammation and malaria settings as follows: 1) the exclusion of subjects with C-reactive protein (CRP) concentrations >5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L, 2) the application of arithmetic correction factors, and 3) the use of a regression correction approach. The impact of adjustment on the estimated prevalence of VAD (defined as inflammation. Depending on the approach used to adjust for inflammation (CRP+AGP), the estimated prevalence of VAD decreased by a median of 11–18 percentage points in PSC compared with unadjusted values. There was no added effect of adjusting for malaria on the estimated VAD after adjusting for CRP and AGP. Conclusions: The use of regression correction (derived from internal data), which accounts for the severity of inflammation, to estimate the prevalence of VAD in PSC in regions with inflammation and malaria is supported by the analysis of the BRINDA data. These findings contribute to the evidence on adjusting for

  4. Forskolin attenuates retinal inflammation in diabetic mice.

    Science.gov (United States)

    You, Zhi-Peng; Xiong, Bin; Zhang, Yu-Lan; Shi, Lu; Shi, Ke

    2018-02-01

    The present study aimed to investigate the effect of forskolin on retinal inflammation under diabetic conditions. C57BL/6 mice were randomly divided into normal control, diabetic control and forskolin treatment groups. The diabetic model was established by intraperitoneal injection of streptozotocin. The forskolin treatment group received intragastrical administration of forskolin for 12 weeks, the other two groups received an equal amount of PBS. At 21 weeks following diabetic induction, an immunoblotting test was conducted to investigate the expression of two inflammatory factors: Intercellular adhesion molecule-1 (ICAM‑1) and tumor necrosis factor‑α (TNF‑α). Glucose concentration was additionally calculated. A leukostasis assay was utilized to compare microvasculature pathological alterations. It was demonstrated that retinal glucose concentration of diabetic control and forskolin treatment were both increased compared with normal control, however the forskolin treatment group was only ~68.06% of the diabetic control due to downregulated glucose transporter 1 expression. The expression of ICAM‑1 and TNF‑α were upregulated in the forskolin treatment and diabetic control groups compared with the normal control, however these two inflammatory factor expression levels in the forskolin treatment group were ~68.75 and 75.37% of diabetic control. It was additionally observed that there were less adherent leukocytes in retinal microvasculature in the forskolin treatment group compared with diabetic control. All the differences observed were significant. Overall, by means of limiting glucose transport into the retina via forskolin, the retinal environment with lower glucose concentration alleviates the inflammatory response under diabetic conditions.

  5. Nasal hyperreactivity and inflammation in allergic rhinitis

    Directory of Open Access Journals (Sweden)

    I. M. Garrelds

    1996-01-01

    Full Text Available The history of allergic disease goes back to 1819, when Bostock described his own ‘periodical affection of the eyes and chest’, which he called ‘summer catarrh’. Since they thought it was produced by the effluvium of new hay, this condition was also called hay fever. Later, in 1873, Blackley established that pollen played an important role in the causation of hay fever. Nowadays, the definition of allergy is ‘An untoward physiologic event mediated by a variety of different immunologic reactions’. In this review, the term allergy will be restricted to the IgE-dependent reactions. The most important clinical manifestations of IgE-dependent reactions are allergic conjunctivitis, allergic rhinitis, allergic asthma and atopic dermatitis. However, this review will be restricted to allergic rhinitis. The histopathological features of allergic inflammation involve an increase in blood flow and vascular permeability, leading to plasma exudation and the formation of oedema. In addition, a cascade of events occurs which involves a variety of inflammatory cells. These inflammatory cells migrate under the influence of chemotactic agents to the site of injury and induce the process of repair. Several types of inflammatory cells have been implicated in the pathogenesis of allergic rhinitis. After specific or nonspecific stimuli, inflammatory mediators are generated from cells normally found in the nose, such as mast cells, antigen-presenting cells and epithelial cells (primary effector cells and from cells recruited into the nose, such as basophils, eosinophils, lymphocytes, platelets and neutrophils (secondary effector cells. This review describes the identification of each of the inflammatory cells and their mediators which play a role in the perennial allergic processes in the nose of rhinitis patients.

  6. Microbiome, inflammation, epigenetic alterations, and mental diseases.

    Science.gov (United States)

    Alam, Reza; Abdolmaleky, Hamid M; Zhou, Jin-Rong

    2017-09-01

    Major mental diseases such as autism, bipolar disorder, schizophrenia, and major depressive disorder are debilitating illnesses with complex etiologies. Recent findings show that the onset and development of these illnesses cannot be well described by the one-gene; one-disease approach. Instead, their clinical presentation is thought to result from the regulative interplay of a large number of genes. Even though the involvement of many genes are likely, up regulating and activation or down regulation and silencing of these genes by the environmental factors play a crucial role in contributing to their pathogenesis. Much of this interplay may be moderated by epigenetic changes. Similar to genetic mutations, epigenetic modifications such as DNA methylation, histone modifications, and RNA interference can influence gene expression and therefore may cause behavioral and neuronal changes observed in mental disorders. Environmental factors such as diet, gut microbiota, and infections have significant role in these epigenetic modifications. Studies show that bioactive nutrients and gut microbiota can alter either DNA methylation and histone signatures through a variety of mechanisms. Indeed, microbes within the human gut may play a significant role in the regulation of various elements of "gut-brain axis," via their influence on inflammatory cytokines and production of antimicrobial peptides that affect the epigenome through their involvement in generating short chain fatty acids, vitamin synthesis, and nutrient absorption. In addition, they may participate in-gut production of many common neurotransmitters. In this review we will consider the potential interactions of diet, gastrointestinal microbiome, inflammation, and epigenetic alterations in psychiatric disorders. © 2017 Wiley Periodicals, Inc.

  7. Oxidative stress and inflammation in liver carcinogenesis

    Directory of Open Access Journals (Sweden)

    Natalia Olaya

    2007-02-01

    Full Text Available

    Inflammation is a common response in the human liver. It is involved in chronic hepatitis, cirrhosis, steatosis, ischemiareperfusion damage, hepatocarcinomas and in the development of metastasis. Reactive oxygen species (ROS production is part of the inflammatory processes. It is implicated in many physiological and pathological situations and can induce mutations in key cancer genes. Normally, this process is prevented by DNA repair enzymatic systems that maintain sequence fidelity during DNA replication. However, overproduction of free radicals in chronic inflammatory diseases is thought to saturate the ability of the cell to repair DNA damage prior to replications. Inflammation-induced genetic damage is not unique to the liver, and it might contribute to the development of mutations in several organs. An example is the chronic inflammatory response in ulcerative colitis that ultimately could lead to neoplasia.

    There is compelling evidence to suggest that most known environmental risk factors for HCC development lead to generation of reactive oxygen species (ROS. Indeed, hepatitis C virus (HCV, alcohol and hepatitis B virus (HBV have all been associated with oxidative stress. Direct production of oxidative stress by HCV core protein has been shown. A link between oxidative stress and liver pathogenesis is also supported by the successful use of antioxidant therapy to treat liver injury caused by chronic HCV infection, although it is not currently used for effective therapy. Ethanol metabolism via the alcohol dehydrogenase pathway and microsomal ethanol oxidizing system contribute substantially to the production of acetaldehyde and generation of ROS. HBx via its association with mitochondria has been shown to induce oxidative stress which in turn leads to activation of a

  8. Airways Disease: Phenotyping Heterogeneity Using Measures of Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Siddiqui Salman

    2007-06-01

    Full Text Available Despite asthma and chronic obstructive pulmonary disease being widely regarded as heterogeneous diseases, a consensus for an accurate system of classification has not been agreed. Recent studies have suggested that the recognition of subphenotypes of airway disease based on the pattern of airway inflammation may be particularly useful in increasing our understanding of the disease. The use of non-invasive markers of airway inflammation has suggested the presence of four distinct phenotypes: eosinophilic, neutrophilic, mixed inflammatory and paucigranulocytic asthma. Recent studies suggest that these subgroups may differ in their etiology, immunopathology and response to treatment. Importantly, novel treatment approaches targeted at specific patterns of airway inflammation are emerging, making an appreciation of subphenotypes particularly relevant. New developments in phenotyping inflammation and other facets of airway disease mean that we are entering an era where careful phenotyping will lead to targeted therapy.

  9. Inflammation and Oxidative Stress in Obesity-Related Glomerulopathy

    Directory of Open Access Journals (Sweden)

    Jinhua Tang

    2012-01-01

    Full Text Available Obesity-related glomerulopathy is an increasing cause of end-stage renal disease. Obesity has been considered a state of chronic low-grade systemic inflammation and chronic oxidative stress. Augmented inflammation in adipose and kidney tissues promotes the progression of kidney damage in obesity. Adipose tissue, which is accumulated in obesity, is a key endocrine organ that produces multiple biologically active molecules, including leptin, adiponectin, resistin, that affect inflammation, and subsequent deregulation of cell function in renal glomeruli that leads to pathological changes. Oxidative stress is also associated with obesity-related renal diseases and may trigger the initiation or progression of renal damage in obesity. In this paper, we focus on inflammation and oxidative stress in the progression of obesity-related glomerulopathy and possible interventions to prevent kidney injury in obesity.

  10. EFFECT OF PICRORHIZA KURROA BENTH. IN ACUTE INFLAMMATION

    OpenAIRE

    Kantibiswas, Tuhin; Marjit, Bani; Maity, Lakshmi Narayan

    1996-01-01

    The effect of the indigenous drug Picrorhiza kurrooa Benth was studied on experimental acute inflammation in rats. It was observed that Picrorhiza kurrooa at a dose of 100 mg/kg b.w. has significant (p

  11. Inflammation, a Link between Obesity and Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Zhaoxia Wang

    2010-01-01

    Full Text Available Obesity, the most common nutritional disorder in industrialized countries, is associated with an increased mortality and morbidity of cardiovascular disease (CVD. Obesity is primarily considered to be a disorder of energy balance, and it has recently been suggested that some forms of obesity are associated with chronic low-grade inflammation. The present paper focuses on the current status of our knowledge regarding chronic inflammation, a link between obesity and CVDs, including heart diseases, vascular disease and atherosclerosis. The paper discusses the methods of body fat evaluation in humans, the endocrinology and distribution of adipose tissue in the genders, the pathophysiology of obesity, the relationship among obesity, inflammation, and CVD, and the adipose tissue-derived cytokines known to affect inflammation. Due to space limitations, this paper focuses on C-reactive protein, serum amyloid A, leptin, adiponectin, resistin, visfatin, chemerin, omentin, vaspin, apelin, and retinol binding protein 4 as adipokines.

  12. Interleukin-17B Antagonizes Interleukin-25-Mediated Mucosal Inflammation.

    Science.gov (United States)

    Reynolds, Joseph M; Lee, Young-Hee; Shi, Yun; Wang, Xiaohu; Angkasekwinai, Pornpimon; Nallaparaju, Kalyan C; Flaherty, Stephanie; Chang, Seon Hee; Watarai, Hiroshi; Dong, Chen

    2015-04-21

    The interleukin-17 (IL-17) family of cytokines has emerged as a critical player in inflammatory diseases. Among them, IL-25 has been shown to be important in allergic inflammation and protection against parasitic infection. Here we have demonstrated that IL-17B, a poorly understood cytokine, functions to inhibit IL-25-driven inflammation. IL-17B and IL-25, both binding to the interleukin-17 receptor B (IL-17RB), were upregulated in their expression after acute colonic inflammation. Individual inhibition of these cytokines revealed opposing functions in colon inflammation: IL-25 was pathogenic but IL-17B was protective. Similarly opposing phenotypes were observed in Citrobacter rodentium infection and allergic asthma. Moreover, IL-25 was found to promote IL-6 production from colon epithelial cells, which was inhibited by IL-17B. Therefore, our data demonstrate that IL-17B is an anti-inflammatory cytokine in the IL-17 family. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. An Interplay between Obesity and Inflammation in Gestational Diabetes Mellitus.

    Science.gov (United States)

    Skórzyńska-Dziduszko, Katarzyna E; Kimber-Trojnar, Żaneta; Patro-Małysza, Jolanta; Olszewska, Anna; Zaborowski, Tomasz; Małecka-Massalska, Teresa

    Gestational diabetes mellitus (GDM) is traditionally defined as hyperglycemia first detected in pregnancy. The risk of GDM is much higher among obese women than in their lean counterparts. An excess of adipose tissue leads to immune and inflammatory responses of both white adipose tissue and the placenta, contributing to systemic inflammation. Although the significance of both obesity and inflammation is relatively well characterized in GDM, the molecular mechanisms involved are not fully defined and require further study. In recent years huge progress has been made in identifying the intracellular signaling pathways involved in the pathophysiology of GDM. However, currently available data regarding inflammation and obesity in women with GDM are still conflicting or incomplete. We discuss selected aspects of the problem and propose future directions for research in the hope of achieving a better understanding of the disease. In particular, this review highlights recent studies exploring molecular alterations related to insulin resistance, inflammation of the adipose tissue and the placenta, lipotoxicity or endotoxemia.

  14. Oxidative Stress and Inflammation: What Polyphenols Can Do for Us?

    Directory of Open Access Journals (Sweden)

    Tarique Hussain

    2016-01-01

    Full Text Available Oxidative stress is viewed as an imbalance between the production of reactive oxygen species (ROS and their elimination by protective mechanisms, which can lead to chronic inflammation. Oxidative stress can activate a variety of transcription factors, which lead to the differential expression of some genes involved in inflammatory pathways. The inflammation triggered by oxidative stress is the cause of many chronic diseases. Polyphenols have been proposed to be useful as adjuvant therapy for their potential anti-inflammatory effect, associated with antioxidant activity, and inhibition of enzymes involved in the production of eicosanoids. This review aims at exploring the properties of polyphenols in anti-inflammation and oxidation and the mechanisms of polyphenols inhibiting molecular signaling pathways which are activated by oxidative stress, as well as the possible roles of polyphenols in inflammation-mediated chronic disorders. Such data can be helpful for the development of future antioxidant therapeutics and new anti-inflammatory drugs.

  15. Lamin-B in systemic inflammation, tissue homeostasis, and aging.

    Science.gov (United States)

    Chen, Haiyang; Zheng, Xiaobin; Zheng, Yixian

    2015-01-01

    Gradual loss of tissue function (or homeostasis) is a natural process of aging and is believed to cause many age-associated diseases. In human epidemiology studies, the low-grade and chronic systemic inflammation in elderly has been correlated with the development of aging related pathologies. Although it is suspected that tissue decline is related to systemic inflammation, the cause and consequence of these aging phenomena are poorly understood. By studying the Drosophila fat body and gut, we have uncovered a mechanism by which lamin-B loss in the fat body upon aging induces age-associated systemic inflammation. This chronic inflammation results in the repression of gut local immune response, which in turn leads to the over-proliferation and mis-differentiation of the intestinal stem cells, thereby resulting in gut hyperplasia. Here we discuss the implications and remaining questions in light of our published findings and new observations.

  16. Relationship between airway pathophysiology and airway inflammation in older asthmatics

    DEFF Research Database (Denmark)

    Porsbjerg, Celeste M; Gibson, Peter G; Pretto, Jeffrey J

    2013-01-01

    BACKGROUND AND OBJECTIVE: Asthma-related morbidity is greater in older compared with younger asthmatics. Airway closure is also greater in older asthmatics, an observation that may be explained by differences in airway inflammation. We hypothesized that in older adult patients with asthma......, neutrophil airway inflammation increases airway closure during bronchoconstriction, while eosinophil airway inflammation increases airway hyperresponsiveness (AHR). METHODS: Asthmatic subjects (n = 26), aged ≥55 years (68% female), were studied, and AHR to 4.5% saline challenge was measured by the response......-dose ratio (%fall in forced expiratory volume in 1 s (FEV1 )/mg saline). Airway closure was assessed during bronchoconstriction percent change in forced vital capacity (FVC)/percent change in FEV1 (i.e. Closing Index). Airway inflammation was assessed by induced sputum and exhaled nitric oxide (eNO). RESULTS...

  17. Light protection of the skin after photodynamic therapy reduces inflammation

    DEFF Research Database (Denmark)

    Petersen, B; Wiegell, S R; Wulf, H C

    2014-01-01

    BACKGROUND: Photodynamic therapy (PDT) is followed by significant inflammation. Protoporphyrin (Pp)IX is still formed in the skin after PDT and patients are sensitive to daylight 24-48 h after treatment. Exposure to daylight after PDT may therefore increase inflammation. OBJECTIVES: To investigate...... whether protection with inorganic sunscreen, foundation or light-blocking plaster after PDT can reduce inflammation caused by daylight-activated PpIX. METHODS: On the right arm of 15 subjects with sun-damaged skin, four identical squares (3 × 3 cm) were given conventional PDT treatment. Immediately after...... (inflammation) were measured with a fluorescence camera and a reflectance meter. RESULTS: PpIX was significantly reduced after artificial daylight illumination (P

  18. OCD May Be Linked to Inflammation in the Brain

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_166829.html OCD May Be Linked to Inflammation in the Brain: Study ... breakthroughs in understanding the biology of OCD, and may lead to the development of new treatments," senior ...

  19. Vasoreactivity, Inflammation and vascular effects of Thiazolidinediones in Insulin resistance

    NARCIS (Netherlands)

    Martens, Fabrice Marcel Anne Clément

    2006-01-01

    In the pathophysiology of atherosclerosis, based on the respons to injury mechanism, the pathophysiological phenomenons endothelial dysfunction and inflammation are playing a pivitol role. Endothelial dysfunction is characterized by a shift towards reduced vasodilation, a pro-inflammatory state,

  20. [Chronic mild inflammation links obesity, metabolic syndrome, atherosclerosis and diabetes].

    Science.gov (United States)

    Andel, M; Polák, J; Kraml, P; Dlouhý, P; Stich, V

    2009-01-01

    Chronic low grade inflammation is relatively new concept in metabolic medicine. This concept describes the relations between the inflammation and adipose tissue, insulin resistence, atherosclerosis and type 2 diabetes mellitus. Macrophages and lymphocytes deposed in adipose tissue produce proinflammatory cytokines which directly or through the CRP liver secretion are targeting endothelial cells, hepatocytes and beta cells of Langerhans islets of pancreas. The dysfunction of these cells follows often further disturbances and in case of beta cells - the cell death. The connection between the adipose tissue insulin resistence, atherosclerosis and type 2 diabetes was earlier described with endocrine and metabolic descriptors. The concept of chronic low grade inflammation creates also another description of multilateral connections in metabolic syndome. The salicylates and the drugs related to them seem to have some glucose lowering properties. The recent development in the field ofchronic low grade inflammation represents also certain therapeutic hope for antiinflammatory intervention in type 2 diabetes.

  1. Inflammation in Achromobacter xylosoxidans infected cystic fibrosis patients

    DEFF Research Database (Denmark)

    Hansen, C. R.; Pressler, T.; Nielsen, K. G.

    2010-01-01

    BACKGROUND: Achromobacter xylosoxidans infection may cause conspicuous chronic pulmonary inflammation in cystic fibrosis (CF) patients similar to Pseudomonas aeruginosa and the Burkholderia cepacia complex (Bcc). Evolution in lung function was compared in chronically infected patients. Cytokine...

  2. Nuclear Imaging of Inflammation in Neurologic and Psychiatric Disorders

    NARCIS (Netherlands)

    de Vries, E.F.J.; Dierckx, R.A.; Klein, H.C.

    2006-01-01

    Cerebral inflammation is a common phenomenon during the progression of neurodegenerative diseases. In general, neurodegenerative diseases have unpredictable clinical courses and timely effective treatment is not available. For effective clinical trials on new drugs, suitable surrogate markers to

  3. Purinergic Receptors: Key Mediators of HIV-1 infection and inflammation

    Directory of Open Access Journals (Sweden)

    Talia H Swartz

    2015-11-01

    Full Text Available Human immunodeficiency virus (HIV-1 causes a chronic infection that afflicts more than 38 million individuals worldwide. While the infection can be suppressed with potent anti-retroviral therapies, individuals infected with HIV have elevated levels of inflammation as indicated by increased T cell activation, soluble biomarkers, and associated morbidity and mortality. A single mechanism linking HIV pathogenesis to this inflammation has yet to be identified. Purinergic receptors are known to mediate inflammation and have been shown to be required for HIV-1 infection at the level of HIV-1 membrane fusion. Here we review the literature on the role of purinergic receptors in HIV-1 infection and associated inflammation and describe a role for these receptors as potential therapeutic targets.

  4. Effects of Ramadan Fasting on the Regulation of Inflammation

    Directory of Open Access Journals (Sweden)

    Safieh Ebrahimi

    2016-03-01

    Full Text Available The month of Ramadan, as a model of intermittent fasting, is a valuable opportunity to investigate the effects of dietary modifications on human metabolism. Fasting improves insulin sensitivity, reduces atherogenic risk, oxidative stress, and inflammation. Inflammation plays a key role in the pathogenesis of different disorders including atherosclerosis, metabolic syndrome and cardiovascular diseases. Ramadan fasting can positively modulate cardiovascular risks and improves the metabolic syndrome features through suppression of inflammatory responses. In this review we attempt to present recent studies that addressed the regulatory role(s of this nutritional status on inflammation in patients with inflammatory diseases. These studies suggest that the anti-inflammatory effect of fasting is significant and could be considered as a complementary therapeutic approach in treatment of inflammatory disorders in patients.Keywords: Ramadan fasting, Inflammation, Metabolic syndrome, Cardiovascular diseaseAbstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract

  5. Inflammation but not dietary macronutrients insufficiency associated with the malnutrition-inflammation score in hemodialysis population.

    Directory of Open Access Journals (Sweden)

    Jie Chen

    Full Text Available Malnutrition is associated with increased risk of mortality in hemodialysis patients. And insufficient dietary intake is the common cause for malnutrition. So, in order to survey the dietary intake of hemodialysis patients and study the relationship between the dietary feature and nutritional status, a cross-sectional study was performed. 75 hemodialysis patients from South China participated in the dietary intake survey and nutrition assessment. A three-day diet diary record was used to estimate the major dietary macronutrients. Nutritional status was assessed by malnutrition-inflammation score (MIS in addition to several related anthropometric measurements. Serum albumin, transferrin, and high-sensitivity C-reactive protein (CRP were measured. Receiver operating characteristic (ROC curve analysis was used to quantify the assessing value of independent parameters for nutritional status. The results showed that 48% patients were malnourished according to the MIS. The malnourished patients had a lower body mass index (BMI, fat mass (FM, albumin and a higher level of CRP, compared with normal nourished patients (P 0.05. The multivariate regression analysis showed that the major macronutrients had no significant association with MIS (P > 0.05. In conclusion, malnutrition is very common in South China hemodialysis population and these data indicated that inflammation but not dietary macronutrients insufficiency might be the candidate cause for malnutrition in hemodialysis population.

  6. Markers of Inflammation and Risk of Coronary Heart Disease

    OpenAIRE

    Nadeem Sarwar; Alexander J. Thompson; Emanuele Di Angelantonio

    2009-01-01

    Cardiovascular disease is the leading cause of global mortality, with coronary heart disease (CHD) its major manifestation. Although inflammation, the body?s response to noxious stimuli, is implicated in several stages of CHD development, the relevance of circulating levels of markers of inflammation to CHD risk remains uncertain. This review summarizes available epidemiological evidence for four emerging inflammatory markers implicated in CHD (fibrinogen, C-reactive protein, lipoprotein-asso...

  7. Oral Inflammatory Diseases and Systemic Inflammation: Role of the Macrophage

    Directory of Open Access Journals (Sweden)

    Hatice eHasturk

    2012-05-01

    Full Text Available Inflammation is a complex reaction to injurious agents and includes vascular responses, migration and activation of leukocytes. Inflammation starts with an acute reaction, which evolves into a chronic phase if allowed to persist unresolved. Acute inflammation is a rapid onset; relatively short process characterized by fluid exudation and emigration of leukocytes, primarily neutrophils, whereas chronic inflammation extends over a longer time and is associated with lymphocyte and macrophage infiltration, blood vessel proliferation, and fibrosis. Inflammation is terminated when the invader is eliminated and the secreted mediators are removed; however, many factors modify the course and morphologic appearance as well as the termination pattern and duration of inflammation. Chronic inflammatory illnesses such as diabetes, arthritis, and heart disease are now seen as problems that might have an impact on the periodontium. Reciprocal effects of periodontal diseases are potential factors modifying severity in the progression of systemic inflammatory diseases. Macrophages are key cells for the inflammatory processes as regulators directing inflammation to chronic pathological changes or resolution with no damage or scar tissue formation. As such, macrophages are involved in a remarkably diverse array of homeostatic processes of vital importance to the host. In addition to their critical role in immunity, macrophages are also widely recognized as ubiquitous mediators of cellular turnover and maintenance of extracellular matrix homeostasis. In this review, our objective is to identify macrophage-mediated events central to the inflammatory basis of chronic diseases, with an emphasis on how extrinsic and intrinsic control of macrophage function can be used to prevent or treat harmful outcomes linked to uncontrolled inflammation.

  8. NITRIC OXIDE INTERFERES WITH HYPOXIA SIGNALING DURING COLONIC INFLAMMATION

    OpenAIRE

    CARIA,Cintia Rabelo e Paiva; MOSCATO,Camila Henrique; TOMÉ,Renata Bortolin Guerra; PEDRAZZOLI Jr,José; RIBEIRO,Marcelo Lima; GAMBERO,Alessandra

    2014-01-01

    Context Intestinal inflammation can induce a local reduction in oxygen levels that triggers an adaptive response centered on the expression of hypoxia-inducible factors (HIFs). Nitric oxide, a well-described inflammatory mediator, may interfere with hypoxia signaling. Objectives We aimed to evaluate the role of nitric oxide in hypoxia signaling during colonic inflammation. Methods Colitis was induced by single (acute) or repeated (reactivated colitis) trinitrobenzenosulfonic acid administ...

  9. Effects of Ramadan Fasting on the Regulation of Inflammation

    OpenAIRE

    Safieh Ebrahimi; Farzad Rahmani; Amir Avan; Mohsen Nematy; Seyyed Mostafa Parizadeh; Seyed Mahdi Hasanian Mehr; Seyed Mohammad Reza Parizadeh

    2016-01-01

    The month of Ramadan, as a model of intermittent fasting, is a valuable opportunity to investigate the effects of dietary modifications on human metabolism. Fasting improves insulin sensitivity, reduces atherogenic risk, oxidative stress, and inflammation. Inflammation plays a key role in the pathogenesis of different disorders including atherosclerosis, metabolic syndrome and cardiovascular diseases. Ramadan fasting can positively modulate cardiovascular risks and improves the metabolic synd...

  10. Voriconazole metabolism is influenced by severe inflammation: a prospective study.

    Science.gov (United States)

    Veringa, Anette; Ter Avest, Mendy; Span, Lambert F R; van den Heuvel, Edwin R; Touw, Daan J; Zijlstra, Jan G; Kosterink, Jos G W; van der Werf, Tjip S; Alffenaar, Jan-Willem C

    2017-01-01

    During an infection or inflammation, several drug-metabolizing enzymes in the liver are down-regulated, including cytochrome P450 iso-enzymes. Since voriconazole is extensively metabolized by cytochrome P450 iso-enzymes, the metabolism of voriconazole can be influenced during inflammation via reduced clearance of the drug, resulting in higher voriconazole trough concentrations. To investigate prospectively the influence of inflammation on voriconazole metabolism and voriconazole trough concentrations. A prospective observational study was performed at the University Medical Center Groningen. Patients were eligible for inclusion if they were ≥18 years old and treated with voriconazole. Voriconazole and voriconazole-N-oxide concentrations were determined in discarded blood samples. To determine the degree of inflammation, C-reactive protein (CRP) concentrations were used. Subsequently, a longitudinal data analysis was performed to assess the effect of inflammation on the metabolic ratio and voriconazole trough concentration. Thirty-four patients were included. In total 489 voriconazole trough concentrations were included in the longitudinal data analysis. This analysis showed that inflammation, reflected by CRP concentrations, significantly influenced the metabolic ratio, voriconazole trough concentration and voriconazole-N-oxide concentration (all P voriconazole metabolism. The metabolic ratio was decreased by 0.99229 N and the voriconazole-N-oxide concentration by 0.99775 N , while the voriconazole trough concentration was increased by 1.005321 N , where N is the difference in CRP units (in mg/L). This study shows that voriconazole metabolism is decreased during inflammation, resulting in higher voriconazole trough concentrations. Therefore, frequent monitoring of voriconazole serum concentrations is recommended during and following severe inflammation. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial

  11. Microglia in the embryonic neocortex - the effect of maternal inflammation

    OpenAIRE

    Swinnen, Nina; Rigato, C.; Brone, Bert; Legendre, P.; Rigo, Jean-Michel

    2010-01-01

    Infection during pregnancy can lead to maternal inflammation. Several studies have suggested that maternal inflammation increases the risk on neuropsychiatric disorders, like autism, in the offspring. The cause of autism remains unknown, it is thought to be a complex interaction of different factors. A study of Vargas et al demonstrated the presence of an active neuroinflammatory process in the brains of autistic patients, with marked microglial cell activation. Microglia colonize the central...

  12. Advances in the imaging of cerebral aneurysm inflammation

    Directory of Open Access Journals (Sweden)

    Michael R Levitt

    2015-06-01

    Full Text Available Cerebral aneurysm formation, growth and rupture are thought to be the result of a complex interaction between cerebrovascular hemodynamics and pathobiology. Recently, new evidence has emerged regarding the role of inflammation in the walls of cerebral aneurysms. Noninvasive methods to characterize the degree of inflammation in aneurysms could enable clinicians to estimate the risk of future aneurysm growth and rupture, influencing treatment. This review examines emerging techniques of imaging inflammatory biomarkers in cerebral aneurysms.

  13. Management of Anemia of Inflammation in the Elderly

    OpenAIRE

    Macciò, Antonio; Madeddu, Clelia

    2012-01-01

    Anemia of any degree is recognized as a significant independent contributor to morbidity, mortality, and frailty in elderly patients. Among the broad types of anemia in the elderly a peculiar role seems to be played by the anemia associated with chronic inflammation, which remains the most complex form of anemia to treat. The origin of this nonspecific inflammation in the elderly has not yet been clarified. It seems more plausible that the oxidative stress that accompanies ageing is the real ...

  14. Obesity, Inflammation, and Lung Injury (OILI): The Good

    OpenAIRE

    Cheryl Wang

    2014-01-01

    Obesity becomes pandemic, predisposing these individuals to great risk for lung injury. In this review, we focused on the anti-inflammatories and addressed the following aspects: adipocytokines and obesity, inflammation and other mechanisms, adipocytokines and lung injury in obesity bridged by inflammation, and potential therapeutic targets. To sum up, the majority of evidence supported that adiponectin, omentin, and secreted frizzled-related protein 5 (SFRP5) were reduced significantly in ob...

  15. THE FIRST BULGARIAN STANDARDIZED SERIES FOR EPICUTANEOUS PATCH TESTING FOR ALLERGIES TO DENTAL MATERIALS AND ALLOYS

    OpenAIRE

    Maria Dencheva; Iliana Stoeva; Angelina Kisselova; Assya Krasteva; Bogdan Petrunov; George Nikolov; Yordan Galabov

    2012-01-01

    The teeth and teeth rows restoration in the maxillofacial area is the last stage of the ongoing patient treatment and a basic purpose for the dental doctors. For this purpose a different set of modern and classic contemporary dental materials is used. The choice of each material during the treatment of every patient with proven allergy to different kind of allergens is very specific and strictly individual. In the everyday oral diagnostics a standardized set of allergens for diagnostics is us...

  16. Genetic Factors in Animal Models of Intestinal Inflammation

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    R Balfour Sartor

    1995-01-01

    Full Text Available The critical importance of host genetic susceptibility in determining chronicity, aggressiveness and complications of intestinal inflammation is clearly demonstrated by studies of inbred rodents, transgenic rats and spontaneous mutants. Inbred Lewis rats challenged by purified bacterial cell wall polymers, indomethacin or small bowel bacterial overgrowth develop chronic granulomatous intestinal inflammation with fibrosis and extraintestinal manifestations, whereas Fischer (major histocompatibility complex identical to Lewis and Buffalo rats identically stimulated demonstrate only self-limited enterocolitis with no chronic inflammation, fibrosis, granulomas or extraintestinal inflammation. Similar differential patterns of intestinal inflammation are apparent in inbred mouse strains challenged with trinitrobenzene-sulphonic acid, Citrobacter freundii or backcrossed with T cell receptor deficient (knockout mice. The dominant role of genetic background in induction of intestinal inflammation is further documented by spontaneous colitis which develops in spontaneously mutant mice, cotton-top tamarins, human leukocyte antigen-B27/ β2 microglobulin transgenic rats and mice with targeted deletions of certain immunoregulatory cytokine and T lymphocyte genes. Identification of the immunological mechanisms of host genetic susceptibility and the genetic basis of spontaneous colitis should provide new insights into the pathogenesis of human inflammatory bowel disease.

  17. Pathogenesis of Myeloproliferative Neoplasms: Role and Mechanisms of Chronic Inflammation

    Directory of Open Access Journals (Sweden)

    Sylvie Hermouet

    2015-01-01

    Full Text Available Myeloproliferative neoplasms (MPNs are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. Recent advances in the biology of MPNs have greatly facilitated their molecular diagnosis since most patients present with mutation(s in the JAK2, MPL, or CALR genes. Yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of MPNs are not fully elucidated. Importantly, chronic inflammation has long been associated with MPN disease and some of the symptoms and complications can be linked to inflammation. Moreover, the JAK inhibitor clinical trials showed that the reduction of symptoms linked to inflammation was beneficial to patients even in the absence of significant decrease in the JAK2-V617F mutant load. These observations suggested that part of the inflammation observed in patients with JAK2-mutated MPNs may not be the consequence of JAK2 mutation. The aim of this paper is to review the different aspects of inflammation in MPNs, the molecular mechanisms involved, the role of specific genetic defects, and the evidence that increased production of certain cytokines depends or not on MPN-associated mutations, and to discuss possible nongenetic causes of inflammation.

  18. Resolution of Sterile Inflammation: Role for Vitamin C

    Directory of Open Access Journals (Sweden)

    Bassem M. Mohammed

    2014-01-01

    Full Text Available Introduction. Macrophage reprogramming is vital for resolution of acute inflammation. Parenteral vitamin C (VitC attenuates proinflammatory states in murine and human sepsis. However information about the mechanism by which VitC regulates resolution of inflammation is limited. Methods. To examine whether physiological levels of VitC modulate resolution of inflammation, we used transgenic mice lacking L-gulono-γ-lactone oxidase. VitC sufficient/deficient mice were subjected to a thioglycollate-elicited peritonitis model of sterile inflammation. Some VitC deficient mice received daily parenteral VitC (200 mg/kg for 3 or 5 days following thioglycollate infusion. Peritoneal macrophages harvested on day 3 or day 5 were examined for intracellular VitC levels, pro- and anti-inflammatory protein and lipid mediators, mitochondrial function, and response to lipopolysaccharide (LPS. The THP-1 cell line was used to determine the modulatory activities of VitC in activated human macrophages. Results. VitC deficiency significantly delayed resolution of inflammation and generated an exaggerated proinflammatory response to in vitro LPS stimulation. VitC sufficiency and in vivo VitC supplementation restored macrophage phenotype and function in VitC deficient mice. VitC loading of THP-1 macrophages attenuated LPS-induced proinflammatory responses. Conclusion. VitC sufficiency favorably modulates macrophage function. In vivo or in vitro VitC supplementation restores macrophage phenotype and function leading to timely resolution of inflammation.

  19. Role of Antioxidants and Natural Products in Inflammation

    Directory of Open Access Journals (Sweden)

    Palanisamy Arulselvan

    2016-01-01

    Full Text Available Inflammation is a comprehensive array of physiological response to a foreign organism, including human pathogens, dust particles, and viruses. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. Recent investigations have clarified that inflammation is a major factor for the progression of various chronic diseases/disorders, including diabetes, cancer, cardiovascular diseases, eye disorders, arthritis, obesity, autoimmune diseases, and inflammatory bowel disease. Free radical productions from different biological and environmental sources are due to an imbalance of natural antioxidants which further leads to various inflammatory associated diseases. In this review article, we have outlined the inflammatory process and its cellular mechanisms involved in the progression of various chronic modern human diseases. In addition, we have discussed the role of free radicals-induced tissue damage, antioxidant defence, and molecular mechanisms in chronic inflammatory diseases/disorders. The systematic knowledge regarding the role of inflammation and its associated adverse effects can provide a clear understanding in the development of innovative therapeutic targets from natural sources that are intended for suppression of various chronic inflammations associated diseases.

  20. Inflammation in Heart Failure: known knowns and unknown unknowns.

    Science.gov (United States)

    Cocco, Giuseppe; Jerie, Paul; Amiet, Philipp; Pandolfi, Stefano

    2017-08-01

    The review deals with inflammation in heart failure (HF). Many data show that systemic inflammation is frequent in HF and implicate that inflammation contributes to damage and dysfunction of the cardiovascular system. Areas Covered: Experimental data have been mainly obtained in acute laboratory animal models. It is questionable whether animals' data can be translated into clinical settings with patients with chronic HF who have concomitant pathologies. The idea of a common inflammatory pathway that characterizes all different forms of clinical HF is unrealistic. It seems realistic that inflammation differs in non-cardiac and cardiac diseases. Research therapeutic options address the use of inhibitors of cytokines, of agents antagonizing oxidative stress, of MMP and of PI3K signaling pathways. Expert Opinion: Considering the many unknowns in our knowledge it is not surprising that early trials aimed to antagonize inflammation in HF have been disappointing. We are far away from having solid therapeutic schedules to use immunomodulation in all subtypes of HF. However, modern trials on HF due to virus infections have proven that immunomodulation is therapeutically effective. We should wisely use the known facts and accept that we have many unknowns. By appropriate selection of the subtypes of HF we may be able to find the appropriate therapy against inflammation in HF.

  1. Pathogenesis of Myeloproliferative Neoplasms: Role and Mechanisms of Chronic Inflammation

    Science.gov (United States)

    Bigot-Corbel, Edith; Gardie, Betty

    2015-01-01

    Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. Recent advances in the biology of MPNs have greatly facilitated their molecular diagnosis since most patients present with mutation(s) in the JAK2, MPL, or CALR genes. Yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of MPNs are not fully elucidated. Importantly, chronic inflammation has long been associated with MPN disease and some of the symptoms and complications can be linked to inflammation. Moreover, the JAK inhibitor clinical trials showed that the reduction of symptoms linked to inflammation was beneficial to patients even in the absence of significant decrease in the JAK2-V617F mutant load. These observations suggested that part of the inflammation observed in patients with JAK2-mutated MPNs may not be the consequence of JAK2 mutation. The aim of this paper is to review the different aspects of inflammation in MPNs, the molecular mechanisms involved, the role of specific genetic defects, and the evidence that increased production of certain cytokines depends or not on MPN-associated mutations, and to discuss possible nongenetic causes of inflammation. PMID:26538820

  2. Inflammation, Immune Activation, and Antiretroviral Therapy in HIV.

    Science.gov (United States)

    Hileman, Corrilynn O; Funderburg, Nicholas T

    2017-06-01

    This review focuses on the differential effects of contemporary antiretrovirals on systemic inflammation as heightened immune activation is linked to important co-morbidities and mortality with HIV infection. Antiretroviral therapy (ART) reduces dramatically systemic inflammation and immune activation, but not to levels synchronous with HIV-uninfected populations. In one ART initiation trial, integrase inhibitors appear to reduce inflammation to a greater degree than non-nucleoside reverse transcriptase inhibitors (NNRTIs); however, it is not clear that there are beneficial effects on inflammation resulting from treatment with integrase inhibitors compared to PIs, between PIs and NNRTIs, between specific nucleoside reverse transcriptase inhibitors, or with maraviroc in ART-naïve patients. In ART switch studies, changing to an integrase inhibitor from a PI-, NNRTI-, or enfuvirtide-containing regimen has resulted in improvement in several markers of inflammation. Additional research is needed to conclusively state whether there are clear differences in effects of specific antiretrovirals on inflammation and immune activation in HIV.

  3. Persistent inflammation on Pap smear: does it warrant evaluation?

    Science.gov (United States)

    Bhutia, K; Puri, M; Gami, N; Aggarwal, K; Trivedi, S S

    2011-01-01

    Due to the low sensitivity of Pap smear, premalignant lesions of the cervix can be missed in women with inflammatory Pap smears. However, it is not practically possible to subject all women with inflammatory Pap smear to colposcopy. This study was carried out with the aim to evaluate whether women with persistent inflammation on Pap smear need further evaluation with colposcopy. Four hundred and twenty women were screened at a tertiary level hospital with Pap smear. Women with inflammation on Pap smear were given treatment as per WHO guidelines and Pap smear was repeated at an interval of 6-12 weeks. Women with persistent inflammation on Pap smear were then subjected to colposcopy and directed biopsy if required. Of the 420 women screened, 102 (24.3%) women had a Pap smear showing inflammation. Thirty six women (8.6%) had persistent inflammatory Pap smear. Thirty women were subjected to colposcopy and 16 (53.3%) had abnormal findings on colposcopy. Five out of these 30 women (16.67%) had Cervical intraepithelial neoplasia (CIN) on biopsy. Nearly 16.67% women with persistent inflammation on Pap smear had cervical intraepithelial neoplasia. Hence, a large number of women with CIN would be missed if persistent inflammation on Pap smear is not evaluated further.

  4. Role of cardiac inflammation in right ventricular failure.

    Science.gov (United States)

    Sun, Xiao-Qing; Abbate, Antonio; Bogaard, Harm-Jan

    2017-10-01

    Right ventricular failure (RVF) is the main determinant of mortality in patients with pulmonary arterial hypertension (PAH). Although the exact pathophysiology underlying RVF remains unclear, inflammation may play an important role, as it does in left heart failure. Perivascular pulmonary artery and systemic inflammation is relatively well studied and known to contribute to the initiation and maintenance of the pulmonary vascular insult in PAH. However, less attention has been paid to the role of cardiac inflammation in RVF and PAH. Consistent with many other types of heart failure, cardiac inflammation, triggered by systemic and local stressors, has been shown in RVF patients as well as in RVF animal models. RV inflammation likely contributes to impaired RV contractility, maladaptive remodelling and a vicious circle between RV and pulmonary vascular injury. Although the potential to improve RV function through anti-inflammatory therapy has not been tested, this approach has been applied clinically in left ventricular failure patients, with variable success. Because inflammation plays a dual role in the development of both pulmonary vascular pathology and RVF, anti-inflammatory therapies may have a potential double benefit in patients with PAH and associated RVF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  5. Role of Antioxidants and Natural Products in Inflammation.

    Science.gov (United States)

    Arulselvan, Palanisamy; Fard, Masoumeh Tangestani; Tan, Woan Sean; Gothai, Sivapragasam; Fakurazi, Sharida; Norhaizan, Mohd Esa; Kumar, S Suresh

    2016-01-01

    Inflammation is a comprehensive array of physiological response to a foreign organism, including human pathogens, dust particles, and viruses. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. Recent investigations have clarified that inflammation is a major factor for the progression of various chronic diseases/disorders, including diabetes, cancer, cardiovascular diseases, eye disorders, arthritis, obesity, autoimmune diseases, and inflammatory bowel disease. Free radical productions from different biological and environmental sources are due to an imbalance of natural antioxidants which further leads to various inflammatory associated diseases. In this review article, we have outlined the inflammatory process and its cellular mechanisms involved in the progression of various chronic modern human diseases. In addition, we have discussed the role of free radicals-induced tissue damage, antioxidant defence, and molecular mechanisms in chronic inflammatory diseases/disorders. The systematic knowledge regarding the role of inflammation and its associated adverse effects can provide a clear understanding in the development of innovative therapeutic targets from natural sources that are intended for suppression of various chronic inflammations associated diseases.

  6. Inflammation laryngeal changes in common cold children

    Directory of Open Access Journals (Sweden)

    E. P. Selkova

    2014-01-01

    Full Text Available This article is dedicated to the connection between laryngealinflammatory pathology and influenza/common cold.The purpose is to study the frequency of different form of laryngitis in children with common cold/ influenza, influenced of carried laryngitis within common cold on laryngeal structures and also the effectiveness of preventive measures against acute respiratory infections.Material and methods are the results of the examination (including laryngeal endoscopy and analysis of medical files of 3169 patients and also the data of the annual report of one Moscow semi-clinic.Results. Inflammation laryngeal pathology was revealed in 152 (4,79% cases, in 129 (84,9% – non-obstructive. 91 patient (59,8% belonged to category “frequently and often sick”. The recurrent episodes were seen in patients with both forms of laryngitis. Different laryngeal pathology (laryngitis, vocal nodules was seen after common cold treatment with 43,5% obstructive and 18,63% non-obstructive laryngitis patient as well as dysphonia in 3-14% getting worse with the following common cold episodes. The preventative measures carried among patients with laryngitis allowed to decrease spreading of this pathology notwithstanding the fact of annual growth of common cold in children.Conclusion. Thus taking to account the high circulation of respiratory viruses the absence of specific preventative measures and the especial role of viruses in development all forms of laryngitis it is recommended to include special drugs in preventative techniques of laryngitis prophylactics. Different methods of non-specific prophylactic are effective in decreasing the amount of common cold episodes, decrease the frequency and severity all forms of laryngitis in children and also tend to stabilize/normalize the voice quality in different laryngeal pathology children.

  7. Glucose transport in brain - effect of inflammation.

    Science.gov (United States)

    Jurcovicova, J

    2014-01-01

    membrane to transport glucose into cells, and GLUT8 from cytosol to rough endoplasmic reticulum to recover redundant glucose to cytosol after protein glycosylation. In autoimmune diseases, the enhanced glucose uptake was found in inflamed peripheral tissue, mainly due to proliferating fibroblasts and activated macrophages. In our experimental model of rheumatoid arthritis (adjuvant arthritis), enhanced 2-deoxy-2[F-18]fluoro-D-glucose was found in the hippocampus and amygdala two days after the induction of the disease which, similarly as in the peripheral joints, can be ascribed to the activated macrophages. The knowledge on the glucose transport and the role of glucose transporters in the brain during systemic autoimmune inflammation is still incomplete and needs further investigations.

  8. The role of inflammation in kidney cancer.

    Science.gov (United States)

    de Vivar Chevez, Antonio Roma; Finke, James; Bukowski, Ronald

    2014-01-01

    MDSC) and positively (TH1 cells, IP-10, and MIG) with tumor progression and survival. Finally, there is a discussion of different inhibitors of inflammation that may be useful in the treatment of RCC.

  9. Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Bettina Schlick

    Full Text Available Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens.Radical prostatectomy specimens of prostate cancer patients (N = 70 were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63 using the Luminex-bead protein array technology.Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin, STX18 (Syntaxin 18 and SPOP (speckle-type POZ protein. Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT, RAB11B and

  10. Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients

    Science.gov (United States)

    Schlick, Bettina; Massoner, Petra; Lueking, Angelika; Charoentong, Pornpimol; Blattner, Mirjam; Schaefer, Georg; Marquart, Klaus; Theek, Carmen; Amersdorfer, Peter; Zielinski, Dirk; Kirchner, Matthias; Trajanoski, Zlatko; Rubin, Mark A.; Müllner, Stefan; Schulz-Knappe, Peter; Klocker, Helmut

    2016-01-01

    Background Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens. Methods Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63) using the Luminex-bead protein array technology. Results Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT

  11. A Feedback Loop between Inflammation and Zn Uptake.

    Directory of Open Access Journals (Sweden)

    Paola Bonaventura

    Full Text Available Zinc (Zn has major effects on the immune system and inflammation is associated with systemic Zn deficiency. The aim of this work was to investigate how inflammation modifies Zn metabolism at the cellular level. Rheumatoid arthritis (RA synoviocytes exposed to cytokines were used as a model of chronic inflammation. Osteoarthritis (OA synoviocytes were used as control.Zn levels were measured in medium and inside cells by Induced Coupled Plasma-Mass Spectrometry (ICP-MS, in the presence of minute quantities of stable spike 70Zn isotope and the addition or not of the pro-inflammatory cytokines interleukin-17 (IL-17 and tumor necrosis factor alpha (TNF-α. Gene expression of ZIP-8 importer, ZnT1 exporter and the homeostasis regulators metallothioneins (MTs was evaluated after pre-exposure to cytokines, with or without exogenous Zn addition at increasing concentrations. IL-6 production was used as a marker of inflammation and measured by ELISA.Exposure to IL-17 and TNF-α enhanced expression of the Zn-importer ZIP-8, regardless of the concentration of Zn in the culture medium. In contrast, the expression of the Zn-exporter ZnT1 and of the MTs was primarily dependent on Zn levels. Addition of Zn also increased the production of IL-6, thus further stimulating the inflammatory response.IL-17/TNF-mediated inflammation enhanced the intracellular Zn uptake by synoviocytes, further increasing inflammation. These observations document the existence of a feedback loop between inflammation and Zn uptake. Based on these results, a mathematical model was developed to represent the cytokine-mediated Zn homeostasis alterations.

  12. Arterial and Cellular Inflammation in Patients with CKD.

    Science.gov (United States)

    Bernelot Moens, Sophie J; Verweij, Simone L; van der Valk, Fleur M; van Capelleveen, Julian C; Kroon, Jeffrey; Versloot, Miranda; Verberne, Hein J; Marquering, Henk A; Duivenvoorden, Raphaël; Vogt, Liffert; Stroes, Erik S G

    2017-04-01

    CKD associates with a 1.5- to 3.5-fold increased risk for cardiovascular disease. Both diseases are characterized by increased inflammation, and in patients with CKD, elevated C-reactive protein level predicts cardiovascular risk. In addition to systemic inflammation, local arterial inflammation, driven by monocyte-derived macrophages, predicts future cardiovascular events in the general population. We hypothesized that subjects with CKD have increased arterial and cellular inflammation, reflected by 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography computed tomography (PET/CT) of the arterial wall and a migratory phenotype of monocytes. We assessed 18 F-FDG uptake in the arterial wall in 14 patients with CKD (mean±SD age: 59±5 years, mean±SD eGFR: 37±12 ml/min per 1.73 m 2 ) but without cardiovascular diseases, diabetes, or inflammatory conditions and in 14 control subjects (mean age: 60±11 years, mean eGFR: 86±16 ml/min per 1.73 m 2 ). Compared with controls, patients with CKD showed increased arterial inflammation, quantified as target-to-background ratio (TBR) in the aorta (TBR max : CKD, 3.14±0.70 versus control, 2.12±0.27; P =0.001) and the carotid arteries (TBR max : CKD, 2.45±0.65 versus control, 1.66±0.27; P inflammation, observed in patients with CKD but without overt atherosclerotic disease and with few traditional risk factors, may contribute to the increased cardiovascular risk associated with CKD. The concomitant elevation of monocyte activity may provide novel therapeutic targets for attenuating this inflammation and thereby preventing CKD-associated cardiovascular disease. Copyright © 2017 by the American Society of Nephrology.

  13. A CONSIDERATION OF BIOMARKERS TO BE USED FOR EVALUATION OF INFLAMMATION IN HUMAN NUTRITIONAL STUDIES

    OpenAIRE

    Calder, P. C.; Marcos, Ascensión

    2013-01-01

    Background and objectives: Inflammation is a normal process and there are a number of cells and mediators involved. They are common to all inflammatory diseases and inflammatory responses, and to both high-grade and low-grade inflammation. Despite great advances linking nutrition to inflammatory processes, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate among acute and chronic inflammation or between the initiation, propagation ...

  14. Radiopharmaceuticals for diagnosis of inflammation; Radiopharmaka fuer die Entzuendungsdiagnostik

    Energy Technology Data Exchange (ETDEWEB)

    Meller, B.; Baehre, M. [Luebeck Univ. (Germany). Klinik fuer Radiologie und Nuklearmedizin

    2007-06-15

    Inflammations represent mediator-induced reactions of the hematopoetic-immunologic cell system resulting from exogenous or endogenous stimuli. On cellular level, an increased expression of inflammatory genes is followed by the release of several mediators. As inflammatory response vascular permeability increases and interstitial oedema develops. Additionally, white blood cells emigrate and several transduction cascades are activated. Radiopharmaceuticals for inflammation scintigraphy should specifically reflect one or several aspects of inflammation pathophysiology on molecular level. A group of elder tracers for this purpose comprised substances that are accumulated due to the permeability of physiological barriers. However, their property to accumulate in all processes with increased vascular permeability results in a comparably low specificity of these methods. In-vitro-labelled granulocytes were the method of choice for scintigraphic imaging of inflammation for years. Investigations with {sup 111}In-labelled granulocytes are still frequently considered as the gold standard to detect inflammation by scintigraphy. The use of antibodies or antibody fragments directed against leucocytes allowed in vivo labelling and substituted more complex techniques of in vitro labelling despite of several disadvantages. Due to the superior imaging quality of positron emission tomography, [{sup 18}F]FDG-labelled leucocytes might result in a renaissance of in vitro methods. In cases of cerebral inflammation, activated microglia was visualised by its increased expression of benzodiazepin receptors. An interesting approach to differentiate between infection and sterile inflammation could be the use of bacterial gyrase inhibitors labelled with radioactive compounds. At present, specificity of this method is still controversially discussed. In search of substances to visualise inflammatory transduction cascades selectively, several chemotactic and chemokinetic cytokines, metabolites

  15. The role of gut inflammation in the pathogenesis of spondyloarthropathies.

    Science.gov (United States)

    Mielants, H; De Vos, M; Cuvelier, C; Veys, E M

    1996-01-01

    The concept of spondyloarthropathy (SpA) gathers together a group of chronic diseases with common clinical, biological, genetic and therapeutic characteristics. The concept forms a distinct entity, different from other rheumatic diseases. The target organs are not only the joint, but also the axial skeleton, the enthesis, the eye, the gut, urogenital tract, the skin and sometimes the heart. The prevalence of this entity in the general population is estimated 1%, equal to the prevalence of rheumatoid arthritis. Genetical predisposition (HLA-B27) is one of the clues to the pathogenesis of the disease. Since reactive arthritis is induced by specific urogenital or enterogenic bacteriae, and since the gut is implicated in different forms of spondyloarthropathies, especially in IBD, it was clear that the gut could play an important role by permitting exogenous factors to enter the body. This hypothesis was the rationale for investigating the gut in the spondyloarthropathies by performing ileocolonoscopies. In the first ileocolonoscopic studies of SpA patients, histological signs of gut inflammation were found in a relatively great number of patients, mostly without any clinical intestinal manifestations. These lesions were not seen in other inflammatory joint diseases. Further ileocolonoscopic studies confirmed the strong relationship between gut and joint inflammation. In patients in whom a second ileocolonoscopy was performed, remission of the joint inflammation was always connected with a disappearance of the gut inflammation, whereas persistence of locomotor inflammation was mostly associated to the persistence of gut inflammation. The hypothesis was proposed that some patients with a spondyloarthropathy had a form of subclinical Crohn's disease in which the locomotor inflammation was the only clinical expression. This hypothesis was confirmed in prospective long-term studies in which the ileocolonoscoped patients were reviewed 2 to 9 years later: about 6% of Sp

  16. Lymphangiogenesis: fuel, smoke, or extinguisher of inflammation's fire?

    Science.gov (United States)

    Abouelkheir, Gabriella R; Upchurch, Bradley D; Rutkowski, Joseph M

    2017-04-01

    Lymphangiogenesis is a recognized hallmark of inflammatory processes in tissues and organs as diverse as the skin, heart, bowel, and airways. In clinical and animal models wherein the signaling processes of lymphangiogenesis are manipulated, most studies demonstrate that an expanded lymphatic vasculature is necessary for the resolution of inflammation. The fundamental roles that lymphatics play in fluid clearance and immune cell trafficking from the periphery make these results seemingly obvious as a mechanism of alleviating locally inflamed environments: the lymphatics are simply providing a drain. Depending on the tissue site, lymphangiogenic mechanism, or induction timeframe, however, evidence shows that inflammation-associated lymphangiogenesis (IAL) may worsen the pathology. Recent studies have identified lymphatic endothelial cells themselves to be local regulators of immune cell activity and its consequential phenotypes - a more active role in inflammation regulation than previously thought. Indeed, results focusing on the immunocentric roles of peripheral lymphatic function have revealed that the basic drainage task of lymphatic vessels is a complex balance of locally processed and transported antigens as well as interstitial cytokine and immune cell signaling: an interplay that likely defines the function of IAL. This review will summarize the latest findings on how IAL impacts a series of disease states in various tissues in both preclinical models and clinical studies. This discussion will serve to highlight some emerging areas of lymphatic research in an attempt to answer the question relevant to an array of scientists and clinicians of whether IAL helps to fuel or extinguish inflammation. Impact statement Inflammatory progression is present in acute and chronic tissue pathologies throughout the body. Lymphatic vessels play physiological roles relevant to all medical fields as important regulators of fluid balance, immune cell trafficking, and immune

  17. Unraveling the Complex Relationship Triad between Lipids, Obesity, and Inflammation

    Directory of Open Access Journals (Sweden)

    Shahida A. Khan

    2014-01-01

    Full Text Available Obesity today stands at the intersection between inflammation and metabolic disorders causing an aberration of immune activity, and resulting in increased risk for diabetes, atherosclerosis, fatty liver, and pulmonary inflammation to name a few. Increases in mortality and morbidity in obesity related inflammation have initiated studies to explore different lipid mediated molecular pathways of attempting resolution that uncover newer therapeutic opportunities of anti-inflammatory components. Majorly the thromboxanes, prostaglandins, leukotrienes, lipoxins, and so forth form the group of lipid mediators influencing inflammation. Of special mention are the omega-6 and omega-3 fatty acids that regulate inflammatory mediators of interest in hepatocytes and adipocytes via the cyclooxygenase and lipoxygenase pathways. They also exhibit profound effects on eicosanoid production. The inflammatory cyclooxygenase pathway arising from arachidonic acid is a critical step in the progression of inflammatory responses. New oxygenated products of omega-3 metabolism, namely, resolvins and protectins, behave as endogenous mediators exhibiting powerful anti-inflammatory and immune-regulatory actions via the peroxisome proliferator-activated receptors (PPARs and G protein coupled receptors (GPCRs. In this review we attempt to discuss the complex pathways and links between obesity and inflammation particularly in relation to different lipid mediators.

  18. Neuropeptides, neurogenic inflammation and complex regional pain syndrome (CRPS).

    Science.gov (United States)

    Birklein, Frank; Schmelz, Martin

    2008-06-06

    This review explains symptoms and nature of neuropeptide signaling and its importance for clinical symptoms of CRPS. Neurogenic inflammation regularly accompanies excitation of primary afferent nociceptors. It has two major components-plasma extravasation and vasodilatation. The most important mediators are the calcitonin gene-related peptide (CGRP) and substance P (SP). After peripheral trauma immune reaction (e.g. cytokines) and the attempts of the tissue to regenerate (e.g. growth factors) sensitize nociceptors and amplify neurogenic inflammation. This cascade of events has been demonstrated in rat models of CRPS. Clinical findings in these animals strongly resemble clinical findings in CRPS, and can be prevented by anti-cytokine and anti-neuropeptide treatment. In CRPS patients, there is meanwhile also plenty of evidence that neurogenic inflammation contributes to clinical presentation. Increased cytokine production was demonstrated, as well as facilitated neurogenic inflammation. Very recently even "non-inflammatory" signs of CRPS (hyperhidrosis, cold skin) have been linked to neuropeptide signaling. Surprisingly, there was even moderately increased neurogenic inflammation in unaffected body regions. This favors the possibility that CRPS patients share genetic similarities. The future search for genetic commonalities will help us to further unravel the "mystery" CRPS.

  19. Metabolic Inflammation-Differential Modulation by Dietary Constituents

    Directory of Open Access Journals (Sweden)

    Claire L. Lyons

    2016-04-01

    Full Text Available Obesity arises from a sustained positive energy balance which triggers a pro-inflammatory response, a key contributor to metabolic diseases such as T2D. Recent studies, focused on the emerging area of metabolic-inflammation, highlight that specific metabolites can modulate the functional nature and inflammatory phenotype of immune cells. In obesity, expanding adipose tissue attracts immune cells, creating an inflammatory environment within this fatty acid storage organ. Resident immune cells undergo both a pro-inflammatory and metabolic switch in their function. Inflammatory mediators, such as TNF-α and IL-1β, are induced by saturated fatty acids and disrupt insulin signaling. Conversely, monounsaturated and polyunsaturated fatty acids do not interrupt metabolism and inflammation to the same extent. AMPK links inflammation, metabolism and T2D, with roles to play in all and is influenced negatively by obesity. Lipid spillover results in hepatic lipotoxicity and steatosis. Also in skeletal muscle, excessive FFA can impede insulin’s action and promote inflammation. Ectopic fat can also affect pancreatic β-cell function, thereby contributing to insulin resistance. Therapeutics, lifestyle changes, supplements and dietary manipulation are all possible avenues to combat metabolic inflammation and the subsequent insulin resistant state which will be explored in the current review.

  20. Inflammation and premature aging in advanced chronic kidney disease.

    Science.gov (United States)

    Kooman, Jeroen P; Dekker, Marijke J; Usvyat, Len A; Kotanko, Peter; van der Sande, Frank M; Schalkwijk, Casper G; Shiels, Paul G; Stenvinkel, Peter

    2017-10-01

    Systemic inflammation in end-stage renal disease is an established risk factor for mortality and a catalyst for other complications, which are related to a premature aging phenotype, including muscle wasting, vascular calcification, and other forms of premature vascular disease, depression, osteoporosis, and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have a direct effect on cellular and tissue function. In addition to uremia-specific causes, such as abnormalities in the phosphate-Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called "inflammaging" in the general population. Potentially relevant, but still somewhat unexplored in this respect, are abnormal or misplaced protein structures, as well as abnormalities in tissue homeostasis, which evoke danger signals through damage-associated molecular patterns, as well as the senescence-associated secretory phenotype. Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserves, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relationship between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences, are discussed. Copyright © 2017 the American Physiological Society.

  1. Inflammation: The Common Pathway of Stress-Related Diseases

    Science.gov (United States)

    Liu, Yun-Zi; Wang, Yun-Xia; Jiang, Chun-Lei

    2017-01-01

    While modernization has dramatically increased lifespan, it has also witnessed that the nature of stress has changed dramatically. Chronic stress result failures of homeostasis thus lead to various diseases such as atherosclerosis, non-alcoholic fatty liver disease (NAFLD) and depression. However, while 75%–90% of human diseases is related to the activation of stress system, the common pathways between stress exposure and pathophysiological processes underlying disease is still debatable. Chronic inflammation is an essential component of chronic diseases. Additionally, accumulating evidence suggested that excessive inflammation plays critical roles in the pathophysiology of the stress-related diseases, yet the basis for this connection is not fully understood. Here we discuss the role of inflammation in stress-induced diseases and suggest a common pathway for stress-related diseases that is based on chronic mild inflammation. This framework highlights the fundamental impact of inflammation mechanisms and provides a new perspective on the prevention and treatment of stress-related diseases. PMID:28676747

  2. Sustained Inflammation Induces Degeneration of the Temporomandibular Joint

    Science.gov (United States)

    Wang, X.D.; Kou, X.X.; Mao, J.J.; Gan, Y.H.; Zhou, Y.H.

    2012-01-01

    The temporomandibular joint (TMJ) undergoes degenerative changes among patients who suffer from arthritis, and yet the pathogenesis of TMJ osteoarthritis and rheumatoid arthritis is poorly understood. We hypothesized that sustained inflammation in the TMJ induces structural abnormalities, and accordingly characterized the disc and synovium in a novel model with double injections of complete Freund’s adjuvant (CFA), using behavioral, morphological, cellular, and molecular assessments. Thirty-five days following double CFA injections in seven-week-old female Sprague-Dawley rats, the disc in the CFA-induced inflammation group demonstrated multiple degenerative changes, including marked thickening, opacity, and deformation. The discs in the CFA group further showed significantly greater wet and net weights, and elevated collagen, aggrecan, and total glycosaminoglycan contents. The synovium in the CFA-induced inflammation group showed marked infiltration of mononucleated cells and accumulated sub-synovial adipose tissue. Both the disc and synovium had significantly higher iNOS and IL-1β mRNA expression than controls (saline injections). These findings are consistent with our hypothesis that sustained TMJ inflammation, even within the presently observed 35 days, may be a predisposing factor for structural abnormalities. Insight into TMJ inflammation and degeneration is anticipated to improve our understanding of the pathogenesis of TMJ arthritis and help design clinically relevant strategies for tissue engineering. PMID:22427270

  3. Increased hypothalamic serotonin turnover in inflammation-induced anorexia.

    Science.gov (United States)

    Dwarkasing, J T; Witkamp, R F; Boekschoten, M V; Ter Laak, M C; Heins, M S; van Norren, K

    2016-05-20

    Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. First, we investigated the response of two hypothalamic neuronal cell lines to TNFα, IL-6 and LPS. Next, we studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6. In vitro, we showed that hypothalamic neurons responded to inflammatory mediators by releasing cytokines. This inflammatory response was associated with an increased serotonin release. Mice injected with TNFα and IL-6 showed decreased food intake, associated with altered expression of inflammation-related genes in the hypothalamus. In addition, hypothalamic serotonin turnover showed to be elevated in treated mice. Overall, our results underline that peripheral inflammation reaches the hypothalamus where it affects hypothalamic serotoninergic metabolism. These hypothalamic changes in serotonin pathways are associated with decreased food intake, providing evidence for a role of serotonin in inflammation-induced anorexia.

  4. Dietary fibre linked to decreased inflammation in overweight minority youth.

    Science.gov (United States)

    Miller, S J; Batra, A K; Shearrer, G E; House, B T; Cook, L T; Pont, S J; Goran, M I; Davis, J N

    2016-02-01

    The objective of this study was to examine the relationship between diet and inflammation, and adiposity in minority youth. The study was designed as a cross-sectional analysis of 142 overweight (≥85th body mass index percentile) Hispanic and African-American adolescents (14-18 years) with the following measures: anthropometrics, adiposity via magnetic resonance imaging, dietary intake via 24-h dietary recalls, and inflammation markers from fasting blood draws utilizing a multiplex panel. Partial correlations were estimated and analysis of covariance (ancova) models fit to examine the relationship among dietary variables, inflammation markers and adiposity measures with the following a priori covariates: Tanner stage, ethnicity, sex, total energy intake, total body fat and total lean mass. Inference based on ancova models showed that the highest tertile of fibre intake (mean intake of 21.3 ± 6.1 g d(-1) ) vs. the lowest tertile of fibre intake (mean intake of 7.4 ± 1.8 g d(-1) ) was associated with 36% lower plasminogen activator inhibitor-1 (P = 0.02) and 43% lower resistin (P = 0.02), independent of covariates. Similar results were seen for insoluble fibre. No other dietary variables included in this study were associated with inflammation markers. These results suggest that increases in dietary fibre could play an important role in lowering inflammation and therefore metabolic disease risk in high-risk minority youth. © 2015 World Obesity.

  5. Metabolic Inflammation-Differential Modulation by Dietary Constituents.

    Science.gov (United States)

    Lyons, Claire L; Kennedy, Elaine B; Roche, Helen M

    2016-04-27

    Obesity arises from a sustained positive energy balance which triggers a pro-inflammatory response, a key contributor to metabolic diseases such as T2D. Recent studies, focused on the emerging area of metabolic-inflammation, highlight that specific metabolites can modulate the functional nature and inflammatory phenotype of immune cells. In obesity, expanding adipose tissue attracts immune cells, creating an inflammatory environment within this fatty acid storage organ. Resident immune cells undergo both a pro-inflammatory and metabolic switch in their function. Inflammatory mediators, such as TNF-α and IL-1β, are induced by saturated fatty acids and disrupt insulin signaling. Conversely, monounsaturated and polyunsaturated fatty acids do not interrupt metabolism and inflammation to the same extent. AMPK links inflammation, metabolism and T2D, with roles to play in all and is influenced negatively by obesity. Lipid spillover results in hepatic lipotoxicity and steatosis. Also in skeletal muscle, excessive FFA can impede insulin's action and promote inflammation. Ectopic fat can also affect pancreatic β-cell function, thereby contributing to insulin resistance. Therapeutics, lifestyle changes, supplements and dietary manipulation are all possible avenues to combat metabolic inflammation and the subsequent insulin resistant state which will be explored in the current review.

  6. Factors involved in inflammation-induced developmental white matter damage.

    Science.gov (United States)

    Stolp, Helen B; Ek, C Joakim; Johansson, Pia A; Dziegielewska, Katarzyna M; Bethge, Nicole; Wheaton, Benjamin J; Potter, Ann M; Saunders, Norman R

    2009-02-27

    Developmental white matter damage is a brain pathology associated with several long-term neurological disorders. An inflammatory insult has been suggested as the major instigating event. This study investigated the relative influence of inflammation, blood-brain barrier permeability and glial ontogeny in white matter damage. Systemic inflammation was induced in Monodelphis domestica (opossum) by serial intraperitoneal injections of lipopolysaccharide at different stages of brain development. Volume of white matter was estimated for the external capsule. Blood-brain barrier permeability was assessed immunocytochemically. Quantitative RT-PCR was used to measure relative levels of mRNA for IL-1beta, IL-6 and COX-2. Developmental changes in numbers and appearance of microglia and astrocytes were estimated. Results showed that in response to systemic inflammation, white matter was reduced in the external capsule during a circumscribed period only. At the same developmental stage blood-brain barrier permeability was altered, cerebral inflammatory response was present and numbers of microglia increased. However, the periods of altered blood-brain barrier permeability and the cerebral inflammatory response were longer than the period of the external capsule's susceptibility to white matter damage, which coincided with the developmental increase in the number of astrocytes in this tract. Thus, the mechanism of white matter damage following systemic inflammation is multifactorial, including cerebral inflammation and breakdown of brain barriers occurring simultaneously at specific stages of glial cell development.

  7. Unraveling the complex relationship triad between lipids, obesity, and inflammation.

    Science.gov (United States)

    Khan, Shahida A; Ali, Ashraf; Khan, Sarah A; Zahran, Solafa A; Damanhouri, Ghazi; Azhar, Esam; Qadri, Ishtiaq

    2014-01-01

    Obesity today stands at the intersection between inflammation and metabolic disorders causing an aberration of immune activity, and resulting in increased risk for diabetes, atherosclerosis, fatty liver, and pulmonary inflammation to name a few. Increases in mortality and morbidity in obesity related inflammation have initiated studies to explore different lipid mediated molecular pathways of attempting resolution that uncover newer therapeutic opportunities of anti-inflammatory components. Majorly the thromboxanes, prostaglandins, leukotrienes, lipoxins, and so forth form the group of lipid mediators influencing inflammation. Of special mention are the omega-6 and omega-3 fatty acids that regulate inflammatory mediators of interest in hepatocytes and adipocytes via the cyclooxygenase and lipoxygenase pathways. They also exhibit profound effects on eicosanoid production. The inflammatory cyclooxygenase pathway arising from arachidonic acid is a critical step in the progression of inflammatory responses. New oxygenated products of omega-3 metabolism, namely, resolvins and protectins, behave as endogenous mediators exhibiting powerful anti-inflammatory and immune-regulatory actions via the peroxisome proliferator-activated receptors (PPARs) and G protein coupled receptors (GPCRs). In this review we attempt to discuss the complex pathways and links between obesity and inflammation particularly in relation to different lipid mediators.

  8. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn [College of Biological Sciences, China Agricultural University, Beijing 100094 (China); National Institute of Biological Sciences, Beijing 102206 (China); Jin, Wei [Institute for Immunology, Tsinghua University, Beijing 100084 (China); Wang, Yuhui [Institute of Cardiovascular Sciences, Health Science Center, Peking University, Beijing 100191 (China); Huang, Huanwei; Li, Jia; Zhang, Cai [National Institute of Biological Sciences, Beijing 102206 (China)

    2016-04-29

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

  9. Management of Anemia of Inflammation in the Elderly

    Directory of Open Access Journals (Sweden)

    Antonio Macciò

    2012-01-01

    Full Text Available Anemia of any degree is recognized as a significant independent contributor to morbidity, mortality, and frailty in elderly patients. Among the broad types of anemia in the elderly a peculiar role seems to be played by the anemia associated with chronic inflammation, which remains the most complex form of anemia to treat. The origin of this nonspecific inflammation in the elderly has not yet been clarified. It seems more plausible that the oxidative stress that accompanies ageing is the real cause of chronic inflammation of the elderly and that the same oxidative stress is actually a major cause of this anemia. The erythropoietic agents have the potential to play a therapeutic role in this patient population. Despite some promising results, rHuEPO does not have a specific indication for the treatment of anemia in the elderly. Moreover, concerns about their side effects have spurred the search for alternatives. Considering the etiopathogenetic mechanisms of anemia of inflammation in the elderly population, an integrated nutritional/dietetic approach with nutraceuticals that can manipulate oxidative stress and related inflammation may prevent the onset of this anemia and its negative impact on patients’ performance and quality of life.

  10. Management of Anemia of Inflammation in the Elderly

    Science.gov (United States)

    Macciò, Antonio; Madeddu, Clelia

    2012-01-01

    Anemia of any degree is recognized as a significant independent contributor to morbidity, mortality, and frailty in elderly patients. Among the broad types of anemia in the elderly a peculiar role seems to be played by the anemia associated with chronic inflammation, which remains the most complex form of anemia to treat. The origin of this nonspecific inflammation in the elderly has not yet been clarified. It seems more plausible that the oxidative stress that accompanies ageing is the real cause of chronic inflammation of the elderly and that the same oxidative stress is actually a major cause of this anemia. The erythropoietic agents have the potential to play a therapeutic role in this patient population. Despite some promising results, rHuEPO does not have a specific indication for the treatment of anemia in the elderly. Moreover, concerns about their side effects have spurred the search for alternatives. Considering the etiopathogenetic mechanisms of anemia of inflammation in the elderly population, an integrated nutritional/dietetic approach with nutraceuticals that can manipulate oxidative stress and related inflammation may prevent the onset of this anemia and its negative impact on patients' performance and quality of life. PMID:23091709

  11. Persistent low-grade inflammation and regular exercise

    DEFF Research Database (Denmark)

    Åström, Maj-brit; Feigh, Michael; Pedersen, Bente Klarlund

    2010-01-01

    Persistent low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes and dementia and evidence exists that inflammation is a causal factor in the development of insulin resistance and atherosclerosis. Regular exercise offers protection...... diabetes and dementia. We suggest that the anti-inflammatory effects of exercise may be mediated via a long-term effect of exercise leading to a reduction in visceral fat mass and/or by induction of anti-inflammatory cytokines with each bout of exercise....... against all of these diseases and recent evidence suggests that the protective effect of exercise may to some extent be ascribed to an anti-inflammatory effect of regular exercise. Visceral adiposity contributes to systemic inflammation and is independently associated with the occurrence of CVD, type 2...

  12. The value of panoramic radiography in assessing maxillary sinus inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Bong Hae; Jung, Yun Hoa; Nah, Kyung Soo [Department of Oral and Maxillofacial Radiology, College of Dentistry, Pusan National University, Pusan (Korea, Republic of)

    2008-12-15

    To evaluate the value of panoramic radiography in diagnosing maxillary sinus inflammation. A total of 214 maxillary sinuses from 114 panoramic radiographs were assessed in this study. Two independent experienced oral radiologists evaluated the images in random order for sinus inflammation. Using Cone beam CT images as the gold standard, the sensitivity and specificity of panoramic radiography were calculated, and inter- and intraobserver agreement for panoramic interpretation were obtained. The mean sensitivity and specificity of panoramic radiography were 81.0% and 85.6%, respectively. The weighted kappas for inter- and intraobserver agreement of panoramic radiography were 0.56 and 0.60, respectively. Panoramic radiography is a reasonably accurate method for diagnosing maxillary sinus inflammation and can be used for screening. However, additional examinations should be considered in patients with potentially significant pathology.

  13. Low birth weight, adult BMI and inflammation in middle age

    DEFF Research Database (Denmark)

    Pedersen, Jolene Lee Masters; Rod, Naja Hulvej; Avlund, Kirsten

    2013-01-01

    This study examines the association between birthweight and adult BMI with inflammation in middle age measured by interleukin 6 (IL- 6), interleukin 10 (IL-10), interleukin 18 (IL-18), high sensitivity Creactive protein (hsCRP) and tumor necrosis factor alpha (tnf-α). The study is based...... on participants with continued participation in the Copenhagen Perinatal cohort and Copenhagen Aging and Midlife Biobank clinical examination (n=1,719). Birthweight was negatively associated with hsCRP and IL-18.No association was identified with tnf-α, IL-6 and IL-10. Adult BMI was positively and significantly...... associated with all measures of inflammation besides IL-10. Finally, participants in both the lowest tertile of birthweight and highest tertile of adult BMI had the highest levels of all inflammatory markers. Low birthweight and high adult BMI are risk factors for inflammation in middle age. While...

  14. Genetic influence on inflammation variables in the elderly

    DEFF Research Database (Denmark)

    de Maat, Moniek P M; Bladbjerg, Else Marie; Hjelmborg, Jacob v. B.

    2004-01-01

    BACKGROUND: Inflammation variables (C-reactive protein [CRP], fibrinogen, and soluble intercellular adhesion molecule-1 [sICAM-1]) have been identified as risk factors for cardiovascular disease. It is still not known how much the regulation of inflammatory risk factors is determined by genetic...... factors, and the aim of this study was to determine the heritability of these inflammation variables and of the acute phase regulating cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) at older ages. METHODS AND RESULTS: The heritability of CRP, fibrinogen, sICAM-1, IL-6, and TNF...... factors accounted for 20% to 55% of the variation in plasma levels of the inflammation variables. The highest heritability was found for sICAM-1. The genetic polymorphisms we studied explained only a small, insignificant part of the heritability. CONCLUSIONS: This study in elderly twins provides evidence...

  15. Chemo-inflammation-an effective treatment for freckles

    Directory of Open Access Journals (Sweden)

    Pasricha J

    1999-01-01

    Full Text Available Freckles are fairly common and considered to be incurable. We have developed a new technique called "Chemo-inflammation" with which we have treated 5 patients (4 girls and one boy having extensive freckles with excellent results. All the freckles disappeared completely from the treated areas and there has been no recurrence so far. The technique consists of applying a liquid based on an alkyl sulphate, on the affected skin and repeating the application every hour for a day till the entire skin develops adequate inflammation. The liquid is then washed off with tap water and the skin is treated with topical (or systemic corticosteroids till the inflammation subsides and the treated skin peels off and attains its normal texture. This generally happens within a week or so. Post-inflammatory hyperpigmemation has to be prevented by adequate anti-inflammatory treatment. Otherwise there are no precautions.

  16. Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis

    Directory of Open Access Journals (Sweden)

    Takayuki Okamoto

    2012-01-01

    Full Text Available Deregulated interplay between inflammation and coagulation plays a pivotal role in the pathogenesis of sepsis. Therapeutic approaches that simultaneously target both inflammation and coagulation hold great promise for the treatment of sepsis. Thrombomodulin is an endogenous anticoagulant protein that, in cooperation with protein C and thrombin-activatable fibrinolysis inhibitor, serves to maintain the endothelial microenvironment in an anti-inflammatory and anticoagulant state. A recombinant soluble form of thrombomodulin has been approved to treat patients suffering from disseminated intravascular coagulation (DIC and has thus far shown greater therapeutic potential than heparin. A phase II clinical trial is currently underway in the USA to study the efficacy of thrombomodulin for the treatment of sepsis with DIC complications. This paper focuses on the critical roles that thrombomodulin plays at the intersection of inflammation and coagulation and proposes the possible existence of interactions with integrins via protein C. Finally, we provide a rationale for the clinical application of thrombomodulin for alleviating sepsis.

  17. Inflammation and Arterial Hypertension: From Pathophysiological Links to Risk Prediction.

    Science.gov (United States)

    Pietri, Panagiota; Vlachopoulos, Charalambos; Tousoulis, Dimitris

    2015-01-01

    Over the last years, ample data have demonstrated the pivotal role of low-grade inflammation in the pathophysiology of atherosclerosis and cardiovascular disease. It is well established that inflammatory activation, serving either as a substrate, in the chronic phase of atherosclerotic disease, or as a trigger, in the acute phase, increases cardiovascular events. Considering hypertension, the inflammatory process is implicated in its pathophysiology through a bidirectional relationship since arterial hypertension may enhance inflammation and vice versa. Inflammatory biomarkers such as high-sensitivity C-reactive protein, have shown predictive value for both the incidence of hypertension and the clinical outcomes in hypertensive patients. In the present review, data on the association between arterial hypertension and low-grade inflammation will be reported and potential pathophysiological pathways and clinical implications underlying this association will be discussed.

  18. Roles of IL-8 in ocular inflammations: a review.

    Science.gov (United States)

    Ghasemi, Hassan; Ghazanfari, Tooba; Yaraee, Roya; Faghihzadeh, Soghrat; Hassan, Zuhair Mohammad

    2011-12-01

    This review presents the current in vitro and in vivo animal and human research on the roles of IL-8 in ocular inflammatory diseases. Data sources were a literature review using Pub Med, Medline, and ISI databases (from 1990 to 2011). Search items included interleukine-8 (IL-8), CXCL8, chemokines, cytokines, alone or in combination with the, serum, aqueous, vitreous, eye, ocular, ocular tissues, ophthalmic, and review. IL-8 may be involved in primary or secondary ocular inflammations. Ocular effects of IL-8 differ based on the source of the secretion and site of the action. The most important effects of IL-8 in the eyes are angiogenic activities and induction of ocular inflammation. IL-8 plays important roles in ocular inflammation and angiogenesis in conjunctiva, cornea, iris, retina, and orbit. Anti-IL-8 targeted immunotherapy has been introduced as an important treatment modality, provided that IL-8 signal blocking takes place in desired areas and tissues.

  19. A distinct bacterial dysbiosis associated skin inflammation in ovine footrot

    Science.gov (United States)

    Maboni, Grazieli; Blanchard, Adam; Frosth, Sara; Stewart, Ceri; Emes, Richard; Tötemeyer, Sabine

    2017-03-01

    Ovine footrot is a highly prevalent bacterial disease caused by Dichelobacter nodosus and characterised by the separation of the hoof horn from the underlying skin. The role of innate immune molecules and other bacterial communities in the development of footrot lesions remains unclear. This study shows a significant association between the high expression of IL1β and high D. nodosus load in footrot samples. Investigation of the microbial population identified distinct bacterial populations in the different disease stages and also depending on the level of inflammation. Treponema (34%), Mycoplasma (29%) and Porphyromonas (15%) were the most abundant genera associated with high levels of inflammation in footrot. In contrast, Acinetobacter (25%), Corynebacteria (17%) and Flavobacterium (17%) were the most abundant genera associated with high levels of inflammation in healthy feet. This demonstrates for the first time there is a distinct microbial community associated with footrot and high cytokine expression.

  20. Pannexin1 as mediator of inflammation and cell death.

    Science.gov (United States)

    Crespo Yanguas, Sara; Willebrords, Joost; Johnstone, Scott R; Maes, Michaël; Decrock, Elke; De Bock, Marijke; Leybaert, Luc; Cogliati, Bruno; Vinken, Mathieu

    2017-01-01

    Pannexins form channels at the plasma membrane surface that establish a pathway for communication between the cytosol of individual cells and their extracellular environment. By doing so, pannexin signaling dictates several physiological functions, but equally underlies a number of pathological processes. Indeed, pannexin channels drive inflammation by assisting in the activation of inflammasomes, the release of pro-inflammatory cytokines, and the activation and migration of leukocytes. Furthermore, these cellular pores facilitate cell death, including apoptosis, pyroptosis and autophagy. The present paper reviews the roles of pannexin channels in inflammation and cell death. In a first part, a state-of-the-art overview of pannexin channel structure, regulation and function is provided. In a second part, the mechanisms behind their involvement in inflammation and cell death are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Angiogenesis and Inflammation in Peritoneal Dialysis: The Role of Adipocytes

    Directory of Open Access Journals (Sweden)

    Jun Shi

    2017-05-01

    Full Text Available Chronic inflammation and angiogenesis are the most common complications in patients undergoing maintenance peritoneal dialysis (PD, resulting in progressive peritoneum remolding and, eventually, utrafiltration failure. Contributing to the deeper tissue under the peritoneal membrane, adipocytes play a neglected role in this process. Some adipokines act as inflammatory and angiogenic promoters, while others have the opposite effects. Adipokines, together with inflammatory factors and other cytokines, modulate inflammation and neovascularization in a coordinated fashion. This review will also emphasize cellular regulators and their crosstalk in long-term PD. Understanding the molecular mechanism, targeting changes in adipocytes and regulating adipokine secretion will help extend therapeutic methods for preventing inflammation and angiogenesis in PD.

  2. Transient band keratopathy associated with ocular inflammation and systemic hypercalcemia

    Directory of Open Access Journals (Sweden)

    Anat Galor

    2008-10-01

    Full Text Available Anat Galor, Henry A Leder, Jennifer E Thorne, James P DunnThe Wilmer Eye Institute, Department of Ophthalmology, the Johns Hopkins University School of MedicinePurpose: To report a case of visually significant band keratopathy associated with ocular inflammation and systemic hypercalcemia which markedly decreased in severity after treatment of these underlying factors.Methods: Retrospective case report.Results: A 53-year-old Asian female with granulomatous panuveitis in the left eye presented with diffuse band keratopathy through the central cornea. The serum calcium was elevated. The patient was treated with topical prednisolone acetate 1% and oral prednisone with marked improvement in inflammation. The band keratopathy lessened in severity with clearing of the central cornea and improvement in visual acuity.Conclusions: Early medical treatment of underlying factors may allow reversal of band keratopathy.Keywords: ocular inflammation, transient band keratopathy

  3. Inflammation and Alzheimer's disease: possible role of periodontal diseases.

    Science.gov (United States)

    Kamer, Angela R; Craig, Ronald G; Dasanayake, Ananda P; Brys, Miroslaw; Glodzik-Sobanska, Lidia; de Leon, Mony J

    2008-07-01

    The molecular and cellular mechanisms responsible for the etiology and pathogenesis of Alzheimer's disease (AD) have not been defined; however, inflammation within the brain is thought to play a pivotal role. Studies suggest that peripheral infection/inflammation might affect the inflammatory state of the central nervous system. Chronic periodontitis is a prevalent peripheral infection that is associated with gram-negative anaerobic bacteria and the elevation of serum inflammatory markers including C-reactive protein. Recently, chronic periodontitis has been associated with several systemic diseases including AD. In this article we review the pathogenesis of chronic periodontitis and the role of inflammation in AD. In addition, we propose several potential mechanisms through which chronic periodontitis can possibly contribute to the clinical onset and progression of AD. Because chronic periodontitis is a treatable infection, it might be a readily modifiable risk factor for AD.

  4. S100 Proteins As an Important Regulator of Macrophage Inflammation

    Directory of Open Access Journals (Sweden)

    Chang Xia

    2018-01-01

    Full Text Available The S100 proteins, a family of calcium-binding cytosolic proteins, have a broad range of intracellular and extracellular functions through regulating calcium balance, cell apoptosis, migration, proliferation, differentiation, energy metabolism, and inflammation. The intracellular functions of S100 proteins involve interaction with intracellular receptors, membrane protein recruitment/transportation, transcriptional regulation and integrating with enzymes or nucleic acids, and DNA repair. The S100 proteins could also be released from the cytoplasm, induced by tissue/cell damage and cellular stress. The extracellular S100 proteins, serving as a danger signal, are crucial in regulating immune homeostasis, post-traumatic injury, and inflammation. Extracellular S100 proteins are also considered biomarkers for some specific diseases. In this review, we will discuss the multi-functional roles of S100 proteins, especially their potential roles associated with cell migration, differentiation, tissue repair, and inflammation.

  5. Persistent low-grade inflammation and regular exercise

    DEFF Research Database (Denmark)

    Astrom, Maj-Briit; Feigh, Michael; Pedersen, Bente Klarlund

    2010-01-01

    Persistent low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes and dementia and evidence exists that inflammation is a causal factor in the development of insulin resistance and atherosclerosis. Regular exercise offers protection...... against all of these diseases and recent evidence suggests that the protective effect of exercise may to some extent be ascribed to an anti-inflammatory effect of regular exercise. Visceral adiposity contributes to systemic inflammation and is independently associated with the occurrence of CVD, type 2...... diabetes and dementia. We suggest that the anti-inflammatory effects of exercise may be mediated via a long-term effect of exercise leading to a reduction in visceral fat mass and/or by induction of anti-inflammatory cytokines with each bout of exercise....

  6. Curcumin, Inflammation, and Chronic Diseases: How Are They Linked?

    Directory of Open Access Journals (Sweden)

    Yan He

    2015-05-01

    Full Text Available It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases.

  7. Key Role of DAMP in Inflammation, Cancer, and Tissue Repair.

    Science.gov (United States)

    Pandolfi, Franco; Altamura, Simona; Frosali, Simona; Conti, Pio

    2016-05-01

    This review aimed to take stock of the current status of research on damage-associated molecular pattern (DAMP) protein. We discuss the Janus-faced role of DAMP molecules in inflammation, cancer, and tissue repair. The high-mobility group box (HMGB)-1 and adenosine triphosphate proteins are well-known DAMP molecules and have been primarily associated with inflammation. However, as we shall see, recent data have linked these molecules to tissue repair. HMGB1 is associated with cancer-related inflammation. It activates nuclear factor kB, which is involved in cancer regulation via its receptor for advanced glycation end-products (RAGE), Toll-like receptors 2 and 4. Proinflammatory activity and tissue repair may lead to pharmacologic intervention, by blocking DAMP RAGE and Toll like receptor 2 and 4 role in inflammation and by increasing their concentration in tissue repair, respectively. We conducted a MEDLINE search for articles pertaining to the various issues related to DAMP, and we discuss the most relevant articles especially (ie, not only those published in journals with a higher impact factor). A cluster of remarkable articles on DAMP have appeared in the literature in recent years. Regarding inflammation, several strategies have been proposed to target HMGB1, from antibodies to recombinant box A, which interacts with RAGE, competing with the full molecule. In tissue repair, it was reported that the overexpression of HMGB1 or the administration of exogenous HMGB1 significantly increased the number of vessels and promoted recovery in skin-wound, ischemic injury. Due to the bivalent nature of DAMP, it is often difficult to explain the relative role of DAMP in inflammation versus its role in tissue repair. However, this point is crucial as DAMP-related treatments move into clinical practice. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  8. CREBH mediates metabolic inflammation to hepatic VLDL overproduction and hyperlipoproteinemia.

    Science.gov (United States)

    Song, Yongyan; Zhao, Miaoyun; Cheng, Xiao; Shen, Jing; Khound, Rituraj; Zhang, Kezhong; Su, Qiaozhu

    2017-08-01

    Metabolic inflammation is closely associated with hyperlipidemia and cardiovascular disease. However, the underlying mechanisms are not fully understood. The current study established that cAMP-responsive-element-binding protein H (CREBH), an acute-phase transcription factor, enhances very-low-density lipoprotein (VLDL) assembly and secretion by upregulating apolipoprotein B (apoB) expression and contributes to metabolic inflammation-associated hyperlipoproteinemia induced by TNFα, lipopolysaccharides (LPS), and high-fat diet (HFD) in mice. Specifically, overexpression of CREBH significantly induced mRNA and protein expression of apoB in McA-7777 cells. Luciferase assay further revealed that the presence of CREBH could significantly increase the activity of the apoB gene promoter. In contrast, genetic depletion of CREBH in mice resulted in significant reduction in expression of hepatic apoB mRNA. Challenging mice with an acute fat load led to upregulation of triglyceride (TG)-rich lipoprotein secretion in wild type mice, but not in CREBH-null mice. TNFα treatment activated hepatic CREBH expression, which in turn enhanced hepatic apoB biosynthesis and VLDL secretion. Metabolic inflammation induced by LPS or HFD also resulted in overproduction of apoB and hyperlipoproteinemia in wild type mice, but not in CREBH-null mice. This study demonstrates that CREBH could be a mediator between metabolic inflammation and hepatic VLDL overproduction in chronic metabolic disorders. This novel finding establishes CREBH as the first transcription factor that regulates apoB expression on the transcriptional level and the subsequent VLDL biosynthesis in response to metabolic inflammation. The study also provides novel insight into the pathogenesis of hyperlipidemia in metabolic syndrome. CREBH mediates inflammatory signaling to VLDL overproduction in metabolic stress. Activation of CREBH in inflammation enhances mRNA and protein expression of apoB. CREBH presents a potential novel

  9. Bacterial Cell Wall Polymer-Induced Granulomatous Inflammation

    Science.gov (United States)

    Sartor; Herfarth; Van Tol EAF

    1996-04-01

    Local or systemic injection of peptidoglycan-polysaccharide polymers, which are the primary structural components of cell walls of nearly all bacteria, leads to acute inflammation, which can develop into chronic, spontaneously relapsing, granulomatous inflammation in a number of organs. Evolution into chronic granulomatous inflammation is dependent upon persistence of poorly biodegradable cell wall polymers within tissues, genetically determined host susceptibility, and generation of a T-lymphocyte-mediated immune response. Intraperitoneal injection of peptidoglycan-polysaccharide fragments from group A streptococci or selected intestinal bacteria into susceptible Lewis rats leads to chronic, spontaneously reactivating erosive arthritis and hepatic granulomas. Subserosal (intramural) injection of poorly biodegradable cell wall fragments into the distal intestine of Lewis rats induces chronic, spontaneously relapsing granulomatous enterocolitis with associated arthritis, hepatic granulomas, anemia, and leukocytosis. Chronic inflammation does not occur in T-lymphocyte-deficient rats and is prevented by cyclosporin-A therapy and degradation of peptidoglycan by the muralytic enzyme, mutanolysin. Moreover, resistant Buffalo and Fischer F344 rats, the latter sharing identical MHC antigens with Lewis rats, develop only acute inflammation with no chronic granulomatous response. Peptidoglycan-polysaccharide polymers activate almost every limb of the inflammatory response. Blockade of specific pathways suggests that interleukin-1, transforming growth factor-beta, plasma kallikrein, and T lymphocytes are dominant mediators of peptidoglycan-polysaccharide-induced arthritis, hepatic granulomas, and enterocolitis. Because of the similarity of immune mechanisms of these rat models to human disease, bacterial cell wall-induced inflammation provides unique opportunities to study pathogenic mechanisms of granuloma formation in response to ubiquitous microbial agents and to test

  10. Markers of Inflammation and Risk of Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Nadeem Sarwar

    2009-01-01

    Full Text Available Cardiovascular disease is the leading cause of global mortality, with coronary heart disease (CHD its major manifestation. Although inflammation, the body’s response to noxious stimuli, is implicated in several stages of CHD development, the relevance of circulating levels of markers of inflammation to CHD risk remains uncertain. This review summarizes available epidemiological evidence for four emerging inflammatory markers implicated in CHD (fibrinogen, C-reactive protein, lipoprotein-associated phospholipase A2 and interleukin-6; considers their likely utility in cardiovascular risk prediction; and outlines areas of outstanding uncertainty.

  11. Histologic features of mesotherapy-induced orbital fat inflammation.

    Science.gov (United States)

    Nabavi, Cameron B; Minckler, Donald S; Tao, Jeremiah P

    2009-01-01

    A 67-year-old man developed acute orbital inflammation after receiving cosmetic mesotherapy (Lipo-Dissolve) to the inferior orbital fat compartments. The injection was intended to cause lipolysis and shrinkage of fat lobules with subsequent cosmetic improvement. Injections of a mixture of bile salts, phospholipid, and alcohol preservative bilaterally in inferior orbital fat lobules led to an acute inflammatory reaction characterized histologically 12 days later by mild lymphocytic infiltration, fat necrosis, and fibrosis in the target areas. Benign proliferation of peripheral nerve trunks consistent with a traumatic neuroma was also noted histologically on one side. Inflammation including fat necrosis and traumatic neuroma are all possible consequences of mesotherapy.

  12. RIP3: a molecular switch for necrosis and inflammation

    Science.gov (United States)

    Moriwaki, Kenta; Chan, Francis Ka-Ming

    2013-01-01

    The receptor-interacting protein kinase 3 (RIP3/RIPK3) has emerged as a critical regulator of programmed necrosis/necroptosis, an inflammatory form of cell death with important functions in pathogen-induced and sterile inflammation. RIP3 activation is tightly regulated by phosphorylation, ubiquitination, and caspase-mediated cleavage. These post-translational modifications coordinately regulate the assembly of a macromolecular signaling complex termed the necrosome. Recently, several reports indicate that RIP3 can promote inflammation independent of its pronecrotic activity. Here, we review our current understanding of the mechanisms that drive RIP3-dependent necrosis and its role in different inflammatory diseases. PMID:23913919

  13. Immunosuppression associated with chronic inflammation in the tumor microenvironment

    Science.gov (United States)

    Wang, Dingzhi; DuBois, Raymond N.

    2015-01-01

    Chronic inflammation contributes to cancer development via multiple mechanisms. One potential mechanism is that chronic inflammation can generate an immunosuppressive microenvironment that allows advantages for tumor formation and progression. The immunosuppressive environment in certain chronic inflammatory diseases and solid cancers is characterized by accumulation of proinflammatory mediators, infiltration of immune suppressor cells and activation of immune checkpoint pathways in effector T cells. In this review, we highlight recent advances in our understanding of how immunosuppression contributes to cancer and how proinflammatory mediators induce the immunosuppressive microenvironment via induction of immunosuppressive cells and activation of immune checkpoint pathways. PMID:26354776

  14. N-3 polyunsaturated fatty acids, body fat and inflammation

    DEFF Research Database (Denmark)

    Lund, Anne-Sofie Quist; Hasselbalch, Ann Louise; Gamborg, Michael

    2013-01-01

    BACKGROUND: Based on animal studies, n-3 polyunsaturated fatty acids (PUFAs) have been suggested to lower the risk of obesity and inflammation. We aimed to investigate if, among humans, intake of n-3 PUFAs was associated with i) total body fat, ii) body fat distribution and iii) obesity-related i......BACKGROUND: Based on animal studies, n-3 polyunsaturated fatty acids (PUFAs) have been suggested to lower the risk of obesity and inflammation. We aimed to investigate if, among humans, intake of n-3 PUFAs was associated with i) total body fat, ii) body fat distribution and iii) obesity...

  15. The Dual Role of Inflammation in Colon Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Carmine Stolfi

    2012-09-01

    Full Text Available Chronic inflammation characterizing patients with inflammatory bowel disease (IBD represents a major risk factor for the development of colorectal cancer. Mechanisms underlying this neoplastic transformation are not fully understood though studies in experimental models of colon carcinogenesis suggest that inflammatory cell-derived cytokines either directly or indirectly stimulate the uncontrolled growth of cancer cells. Nevertheless, under specific inflammatory conditions, immune cells can boost an anti-tumor immune response with the down-stream effect of eliminating dysplastic and cancerous cells. This review outlines the beneficial and detrimental role of inflammation in colon carcinogenesis.

  16. Subclinical inflammation in obese women with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Dina Gamal Eldeen Y. Elkholi

    2012-09-01

    Conclusion: PCOS and controls with andriod obesity had higher levels of pro-inflammatory biomarkers and lower levels of anti-inflammatory biomarkers than PCOS and controls with gynoid obesity. The former groups had IR/HI and metabolic disorders of carbohydrate and lipid metabolism while the latter groups had NIS and normal metabolism. It seems that these metabolic disorders are induced by android obesity with subclinical inflammation of the expanded visceral adipose tissue rather than PCOS per se. The PCOS per se is not associated with subclinical inflammation.

  17. Inflammation-Stimulated Mesenchymal Stromal Cell-Derived Extracellular Vesicles Attenuate Inflammation.

    Science.gov (United States)

    Harting, Matthew T; Srivastava, Amit K; Zhaorigetu, Siqin; Bair, Henry; Prabhakara, Karthik S; Toledano Furman, Naama E; Vykoukal, Jody V; Ruppert, Katherine A; Cox, Charles S; Olson, Scott D

    2018-01-01

    Extracellular vesicles (EVs) secreted by mesenchymal stromal cells (MSCs) have been proposed to be a key mechanistic link in the therapeutic efficacy of cells in response to cellular injuries through paracrine effects. We hypothesize that inflammatory stimulation of MSCs results in the release of EVs that have greater anti-inflammatory effects. The present study evaluates the immunomodulatory abilities of EVs derived from inflammation-stimulated and naive MSCs (MSCEv + and MSCEv, respectively) isolated using a current Good Manufacturing Practice-compliant tangential flow filtration system. Detailed characterization of both EVs revealed differences in protein composition, cytokine profiles, and RNA content, despite similarities in size and expression of common surface markers. MSCEv + further attenuated release of pro-inflammatory cytokines in vitro when compared to MSCEv, with a distinctly different pattern of EV-uptake by activated primary leukocyte subpopulations. The efficacy of EVs was partially attributed to COX2/PGE 2 expression. The present study demonstrates that inflammatory stimulation of MSCs renders release of EVs that have enhanced anti-inflammatory properties partially due to COX2/PGE 2 pathway alteration. Stem Cells 2018;36:79-90. © 2017 AlphaMed Press.

  18. Colorectal Oncogenesis and Inflammation in a Rat Model Based on Chronic Inflammation due to Cycling DSS Treatments

    Directory of Open Access Journals (Sweden)

    Åsa Håkansson

    2011-01-01

    Full Text Available Inflammation is known to be linked with development of colorectal cancer, and the aim was to assess the malignant potential and degree of inflammation in a dextran-sulphate-sodium-(DSS- induced cyclic colonic tumour model (CTM in rats and to compare it with the azoxymethane-(AOM- induced CTM model. Tumours developed in both groups, although, in the DSS group, the colonic mucosa appeared edematous and the number of haemorrhagic erosions and quantity of dysplastic lesions were higher as well as the mucosal concentration of myeloperoxidase and faecal viable count of Enterobacteriaceae. The livers were affected as evaluated by steatosis, parenchymal loss, haemorrhage, and inflammatory infiltrations, and higher proportions of acetate and lower proportions of butyrate in colonic content were found. The DSS model seems to mimic the clinical situation and may be valuable for investigation of inflammation-related dysplasia and colon cancer, as well as for altered liver function by endogenous inflammatory mediators.

  19. Inflammation in CRPS: role of the sympathetic supply.

    Science.gov (United States)

    Schlereth, Tanja; Drummond, Peter D; Birklein, Frank

    2014-05-01

    Acute Complex Regional Pain Syndrome (CRPS) is associated with signs of inflammation such as increased skin temperature, oedema, skin colour changes and pain. Pro-inflammatory cytokines (tumour necrosis factor-α (TNF-α), interleukin-2 (IL-2), IL-1beta, IL-6) are up-regulated, whereas anti-inflammatory cytokines (IL-4, IL-10) are diminished. Adaptive immunity seems to be involved in CRPS pathophysiology as many patients have autoantibodies directed against β2 adrenergic and muscarinic-2 receptors. In an animal tibial fracture model changes in the innate immune response such as up-regulation of keratinocytes are also found. Additionally, CRPS is accompanied by increased neurogenic inflammation which depends mainly on neuropeptides such as CGRP and Substance P. Besides inflammatory signs, sympathetic nervous system involvement in CRPS results in cool skin, increased sweating and sympathetically-maintained pain. The norepinephrine level is lower in the CRPS-affected than contralateral limb, but sympathetic sprouting and up-regulation of alpha-adrenoceptors may result in an adrenergic supersensitivity. The sympathetic nervous system and inflammation interact: norepinephrine influences the immune system and the production of cytokines. There is substantial evidence that this interaction contributes to the pathophysiology and clinical presentation of CRPS, but this interaction is not straightforward. How inflammation in CRPS might be exaggerated by sympathetic transmitters requires further elucidation. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Fatty-acid-mediated hypothalamic inflammation and epigenetic programming.

    Science.gov (United States)

    Cesar, Helena C; Pisani, Luciana Pellegrini

    2017-04-01

    A high-fat diet is the main environmental cue that has been studied in the hypothalamus since the discovery of its connection with hypothalamic inflammation. Current evidence shows hypothalamic inflammation as a likely mechanism for the dysregulation on the homeostatic control of energy balance, which leads to metabolic alterations and obesity. Although this mechanism seems to be reversible when set during adulthood, we argue whether dietary fatty acids, during critical periods of development, could affect hypothalamic function permanently and set an increased susceptibility to obesity. We found few experimental studies that looked at programming induced by different fatty acids on the hypothalamus. They clearly showed a connection between maternal fat diet, hypothalamic inflammation and metabolic alterations in the offspring. We found that not only a high-fat diet but also a normolipidic diet with unbalanced quantities of different fatty acids produced diverse inflammatory responses on the hypothalamus. Therefore, strategies of manipulating dietary fatty acids in pregnant and lactating women may have great impact on the population's future health. However, more research is still needed on the effects of fatty acids and the hypothalamic inflammation on programming. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Ghrelin receptor regulates adipose tissue inflammation in aging.

    Science.gov (United States)

    Lin, Ligen; Lee, Jong Han; Buras, Eric D; Yu, Kaijiang; Wang, Ruitao; Smith, C Wayne; Wu, Huaizhu; Sheikh-Hamad, David; Sun, Yuxiang

    2016-01-01

    Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr(-/-) mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsrp(-/-) mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsrp(-/-) mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance.

  2. Cytoplasmic chromatin triggers inflammation in senescence and cancer.

    Science.gov (United States)

    Dou, Zhixun; Ghosh, Kanad; Vizioli, Maria Grazia; Zhu, Jiajun; Sen, Payel; Wangensteen, Kirk J; Simithy, Johayra; Lan, Yemin; Lin, Yanping; Zhou, Zhuo; Capell, Brian C; Xu, Caiyue; Xu, Mingang; Kieckhaefer, Julia E; Jiang, Tianying; Shoshkes-Carmel, Michal; Tanim, K M Ahasan Al; Barber, Glen N; Seykora, John T; Millar, Sarah E; Kaestner, Klaus H; Garcia, Benjamin A; Adams, Peter D; Berger, Shelley L

    2017-10-19

    Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders.

  3. Systemic inflammation and microglial activation: systematic review of animal experiments

    NARCIS (Netherlands)

    Hoogland, Inge C. M.; Houbolt, Carin; van Westerloo, David J.; van Gool, Willem A.; van de Beek, Diederik

    2015-01-01

    Animal studies show that peripheral inflammatory stimuli may activate microglial cells in the brain implicating an important role of microglia in sepsis-associated delirium. We systematically reviewed animal experiments related to the effects of systemic inflammation on the microglial and

  4. Role of T2 inflammation biomarkers in severe asthma

    NARCIS (Netherlands)

    Parulekar, Amit D.; Diamant, Zuzana; Hanania, Nicola A.

    Purpose of reviewSevere asthma is a heterogeneous syndrome. Classification of asthma into phenotypes and endotypes can improve understanding and treatment of the disease. Identification and utilization of biomarkers, particularly those linked to T2 inflammation, can help group patients into

  5. EFFECT OF PICRORHIZA KURROA BENTH. IN ACUTE INFLAMMATION

    Science.gov (United States)

    Kantibiswas, Tuhin; Marjit, Bani; Maity, Lakshmi Narayan

    1996-01-01

    The effect of the indigenous drug Picrorhiza kurrooa Benth was studied on experimental acute inflammation in rats. It was observed that Picrorhiza kurrooa at a dose of 100 mg/kg b.w. has significant (p<0.01) anti inflammatory effect with respect to control, vehicle and standard drug. PMID:22556764

  6. The role of CB1 in intestinal permeability and inflammation.

    Science.gov (United States)

    Karwad, Mustafa A; Couch, Daniel G; Theophilidou, Elena; Sarmad, Sarir; Barrett, David A; Larvin, Michael; Wright, Karen L; Lund, Jonathan N; O'Sullivan, Saoirse E

    2017-08-01

    The endocannabinoid system has previously been shown to play a role in the permeability and inflammatory response of the human gut. The goal of our study was to determine the effects of endogenous anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) on the permeability and inflammatory response of intestinal epithelium under normal, inflammatory, and hypoxic conditions. Human intestinal mucosa was modeled using Caco-2 cells. Human tissue was collected from planned colorectal resections. Accumulation of AEA and 2-AG was achieved by inhibiting their metabolizing enzymes URB597 (a fatty acid amide hydrolase inhibitor) and JZL184 (a monoacylglycerol lipase inhibitor). Inflammation and ischemia were simulated with TNF-α and IFN-γ and oxygen deprivation. Permeability changes were measured by transepithelial electrical resistance. The role of the CB1 receptor was explored using CB1-knockdown (CB1Kd) intestinal epithelial cells. Endocannabinoid levels were measured using liquid chromatography-mass spectrometry. Cytokine secretion was measured using multiplex and ELISA. URB597 and JZL184 caused a concentration-dependent increase in permeability via CB1 (P permeability via CB1 (P permeability caused by inflammation and hypoxia (P permeability response to inflammation (P permeability and in inflammatory and hypoxic conditions.-Karwad, M. A., Couch, D. G., Theophilidou, E., Sarmad, S., Barrett, D. A., Larvin, M., Wright, K. L., Lund, J. N., O'Sullivan, S. E. The role of CB1 in intestinal permeability and inflammation. © FASEB.

  7. Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy.

    Science.gov (United States)

    Cantin, André M; Hartl, Dominik; Konstan, Michael W; Chmiel, James F

    2015-07-01

    Lung disease is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). Although CF lung disease is primarily an infectious disorder, the associated inflammation is both intense and ineffective at clearing pathogens. Persistent high-intensity inflammation leads to permanent structural damage of the CF airways and impaired lung function that eventually results in respiratory failure and death. Several defective inflammatory responses have been linked to cystic fibrosis transmembrane conductance regulator (CFTR) deficiency including innate and acquired immunity dysregulation, cell membrane lipid abnormalities, various transcription factor signaling defects, as well as altered kinase and toll-like receptor responses. The inflammation of the CF lung is dominated by neutrophils that release oxidants and proteases, particularly elastase. Neutrophil elastase in the CF airway secretions precedes the appearance of bronchiectasis, and correlates with lung function deterioration and respiratory exacerbations. Anti-inflammatory therapies are therefore of particular interest for CF lung disease but must be carefully studied to avoid suppressing critical elements of the inflammatory response and thus worsening infection. This review examines the role of inflammation in the pathogenesis of CF lung disease, summarizes the results of past clinical trials and explores promising new anti-inflammatory options. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  8. Grouping nanomaterials to predict their potential to induce pulmonary inflammation

    NARCIS (Netherlands)

    Braakhuis, Hedwig M|info:eu-repo/dai/nl/371685028; Oomen, Agnes G; Cassee, Flemming R|info:eu-repo/dai/nl/143038990

    2016-01-01

    The rapidly expanding manufacturing, production and use of nanomaterials have raised concerns for both worker and consumer safety. Various studies have been published in which induction of pulmonary inflammation after inhalation exposure to nanomaterials has been described. Nanomaterials can vary in

  9. Polyopes affinis alleviates airway inflammation in a murine model of ...

    Indian Academy of Sciences (India)

    Marine algae have been utilized in food as well as medicine products for a variety of purposes. The purpose of this study was to determine whether an ethanol extract of Polyopes affinis (P.affinis) can inhibit the pathogenesis of T helper 2 (Th2)-mediated allergen-induced airway inflammation in a murine model of asthma.

  10. The endocannabinoid system: an emerging key player in inflammation

    NARCIS (Netherlands)

    Witkamp, R.F.; Meijerink, J.

    2014-01-01

    Purpose of review: The purpose of this review is to illustrate the expanding view of the endocannabinoid system (ECS) in relation to its roles in inflammation. Recent findings: According to the formal classification, the ECS consists of two cannabinoid receptors, their endogenous fatty acid-derived

  11. Inflammation and Immune Response in COPD: Where Do We Stand?

    Directory of Open Access Journals (Sweden)

    Nikoletta Rovina

    2013-01-01

    Full Text Available Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD. Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD. Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs to release “danger signal”. These signals act as ligands to Toll-like receptors (TLRs, triggering the production of cytokines and inducing innate inflammation. In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells. Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs. Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD. This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD.

  12. Biological evaluation of nutraceuticals affecting cartilage metabolism and inflammation

    NARCIS (Netherlands)

    Hartog, A.

    2010-01-01

    Osteoarthritis is the most common joint disease and an important cause of physical disability. Clinical symptoms are frequently associated with a significant functional impairment and signs and symptoms of inflammation, including pain, stiffness and loss of mobility. In osteoarthritis the balance

  13. Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation

    Directory of Open Access Journals (Sweden)

    Rita I. Issa

    2012-05-01

    Full Text Available Obesity is a significant risk factor for developing osteoarthritis in weight-bearing and non-weight-bearing joints. Although the pathogenesis of obesity-associated osteoarthritis is not completely understood, recent studies indicate that pro-inflammatory metabolic factors contribute to an increase in osteoarthritis risk. Adipose tissue, and in particular infrapatellar fat, is a local source of pro-inflammatory mediators that are increased with obesity and have been shown to increase cartilage degradation in cell and tissue culture models. One adipokine in particular, leptin, may be a critical mediator of obesity-associated osteoarthritis via synergistic actions with other inflammatory cytokines. Biomechanical factors may also increase the risk of osteoarthritis by activating cellular inflammation and promoting oxidative stress. However, some types of biomechanical stimulation, such as physiologic cyclic loading, inhibit inflammation and protect against cartilage degradation. A high percentage of obese individuals with knee osteoarthritis are sedentary, suggesting that a lack of physical activity may increase the susceptibility to inflammation. A more comprehensive approach to understanding how obesity alters daily biomechanical exposures within joint tissues may provide new insight into the protective and damaging effects of biomechanical factors on inflammation in osteoarthritis.

  14. Voriconazole metabolism is influenced by severe inflammation: a prospective study

    NARCIS (Netherlands)

    Veringa, A.; Avest, M. Ter; Span, L.F.; Heuvel, E.R. van den; Touw, D.J.; Zijlstra, J.G.; Kosterink, J.G.W.; Werf, T.S. van der; Alffenaar, J.C.

    2017-01-01

    BACKGROUND: During an infection or inflammation, several drug-metabolizing enzymes in the liver are down-regulated, including cytochrome P450 iso-enzymes. Since voriconazole is extensively metabolized by cytochrome P450 iso-enzymes, the metabolism of voriconazole can be influenced during

  15. Osteitis and mucosal inflammation in a rabbit model of sinusitis.

    Science.gov (United States)

    Campos, Carlos Augusto Correia de; Dolci, Eduardo Landini Lutaif; Silva, Leonardo da; Dolci, José Eduardo Lutaif; Campos, Carlos Alberto Herrerias de; Dolci, Ricardo Landini Lutaif

    2015-01-01

    Several experimental studies have shown osteitis after the onset of sinusitis, supporting the idea that bone involvement could participate in the dissemination and perpetuation of this inflammatory disease. However, procedures commonly performed for the induction of sinusitis, such as antrostomies, can trigger sinusitis by themselves. To evaluate osteitis in an animal model of sinusitis that does not violate the sinus directly and verify whether this is limited to the induction side, or if it affects the contralateral side. Experimental study in which sinusitis was produced by inserting an obstructing sponge into the nasal cavity of 20 rabbits. After defined intervals, the animals were euthanized and maxillary sinus samples were removed for semi-quantitative histological analysis of mucosa and bone. Signs of bone and mucosal inflammation were observed, affecting both the induction and contralateral sides. Statistical analysis showed correlation between the intensity of osteitis on both sides, but not between mucosal and bone inflammation on the same side, supporting the theory that inflammation can spread through bone structures, regardless of mucosal inflammation. This study demonstrated that in an animal model of sinusitis that does not disturb the sinus directly osteitis occurs in the affected sinus and that it also affects the contralateral side. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  16. Cardiopulmonary Exercise Capacity and Preoperative Markers of Inflammation

    Directory of Open Access Journals (Sweden)

    Pervez Sultan

    2014-01-01

    Full Text Available Explanatory mechanisms for the association between poor exercise capacity and infections following surgery are underexplored. We hypothesized that aerobic fitness—assessed by cardiopulmonary exercise testing (CPET—would be associated with circulating inflammatory markers, as quantified by the neutrophil-lymphocyte ratio (NLR and monocyte subsets. The association between cardiopulmonary reserve and inflammation was tested by multivariable regression analysis with covariates including anaerobic threshold (AT and malignancy. In a first cohort of 240 colorectal patients, AT was identified as the sole factor associated with higher NLR (P=0.03 and absolute and relative lymphopenia (P=0.01. Preoperative leukocyte subsets and monocyte CD14+ expression (downregulated by endotoxin and indicative of chronic inflammation were also assessed in two further cohorts of age-matched elective gastrointestinal and orthopaedic surgical patients. Monocyte CD14+ expression was lower in gastrointestinal patients (n=43 compared to age-matched orthopaedic patients (n=31. The circulating CD14+CD16− monocyte subset was reduced in patients with low cardiopulmonary reserve. Poor exercise capacity in patients without a diagnosis of heart failure is independently associated with markers of inflammation. These observations suggest that preoperative inflammation associated with impaired cardiorespiratory performance may contribute to the pathophysiology of postoperative outcome.

  17. Inflammation and intracranial aneurysms: mechanisms of initiation, growth, and rupture

    Directory of Open Access Journals (Sweden)

    Peter S Amenta

    2015-06-01

    Full Text Available Outcomes following aneurysmal subarachnoid hemorrhage remain poor in many patients, despite advances in microsurgical and endovascular management. Consequently, considerable effort has been placed in determining the mechanisms of aneurysm formation, growth, and rupture. Various environmental and genetic factors are implicated as key components in the aneurysm pathogenesis. Currently, sufficient evidence exists to incriminate the inflammatory response as the common pathway leading to aneurysm generation and rupture. Central to this model is the interaction between the vessel wall and inflammatory cells. Dysfunction of the endothelium and vascular smooth muscle cells (VSMCs promotes a chronic pathological inflammatory response that progressively weakens the vessel wall. We review the literature pertaining to the cellular and chemical mechanisms of inflammation that contribute to aneurysm development. Hemodynamic stress and alterations in blood flow are discussed regarding their role in promoting chronic inflammation. Endothelial cell and VSMC dysfunction are examined concerning vascular remodeling. The contribution of inflammatory cytokines, especially tumor necrosis factor-α is illustrated. Inflammatory cell infiltration, particularly macrophage-mediated deterioration of vascular integrity, is reviewed. We discuss the inflammation as a means to determine aneurysms at greatest risk of rupture. Finally, future therapeutic implications of pharmacologic modulation of the inflammation are discussed.

  18. Eleutheroside E inhibits doxorubicin-induced inflammation and ...

    African Journals Online (AJOL)

    Purpose: To identify the effects of eleutheroside E (EE) on apoptosis and inflammation induced by doxorubicin (DOX) in H9c2 cells and to investigate the underlying mechanisms. Methods: The effect of EE on H9c2 cell viability was determined using Cell Counting Kit-8 (CCK8). EE effect on DOX-induced apoptosis and ...

  19. Mitigation of monocyte inflammation by inhibition of sodium ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of sodium phosphate co-transporter (Pit-1) on the regulation of monocyte inflammation in diabetic nephropathy uremia (DNU) patients and the underlying principles of inflammatory immune response during DNU pathogenesis. Methods: The levels of CD14+ CD16+ and Pit-1 on peripheral ...

  20. Inflammation: the foundation of diseases and disorders. A review of ...

    African Journals Online (AJOL)

    Great interest in herbal medicine as a potential source of phytopharmaceuticals has created the need to review common factors responsible for major diseases and body disorders. This review shows one such common factor in inflammation and the role herbal medicine can play. Traditional medicinal herbal remedies in the ...

  1. Neurogenic inflammation and allergy | Mostafa | Egyptian Journal of ...

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 7, No 2 (2009) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Neurogenic inflammation and ...

  2. Mutation-promoting molecular networks of uncontrolled inflammation.

    Science.gov (United States)

    Zhang, Hui; Xu, Xuanfu

    2017-06-01

    More and more studies show that chronic inflammation can lead to tumor formation. The complex interactions of inflammatory cells, stroma and tumor parenchymal cell are closely related to tumor formation. Under the state of chronic inflammatory microenvironment, long-term interaction of inflammatory cells and stromal cells as well as the parenchymal cells makes signaling pathway in parenchyma cells disordered. A series of gene level editor modification, epigenetic changes, and the regulation of transcription and translation changes will happen based on signaling pathway disorder. The changes ultimately lead to cell mutations and phenotypic transformation occurred. Recent findings provide an objective basis for cancer treatment and prevention. However, further discusses at the core of the possible molecular in tumor formation provide a theoretical foundation for future study of the pathogenesis and molecular targeted therapy of cancer. This review summarizes the research in the field of chronic inflammation and cancer in recent years, and analyze the molecules network in the process of the carcinogenic inflammation comprehensively. Beyond that, this review intends to describe possible carcinogenic inflammation core molecular and provides a theoretical basis for future study of the pathogenesis, chemoprevention and molecular targeted therapy of cancer.

  3. S100A4, a link between metastasis and inflammation

    DEFF Research Database (Denmark)

    Ambartsumian, N.; Grigorian, M.

    2016-01-01

    Chronic inflammation is acknowledged to be a hallmark of neoplasia—both in cancer initiation and metastasis progression. Here we summarise data suggesting that S100A4 is а trigger of the cascade events that establish an inflammatory milieu and provide a potent flame for primary tumour growth...

  4. The role of inflammation in the pathogenesis of glaucoma

    DEFF Research Database (Denmark)

    Vohra, Rupali; Tsai, James C; Kolko, Miriam

    2013-01-01

    Glaucoma is an ocular disorder characterized by the progressive loss of retinal ganglion cells (RGC) and their axons. There are various hypotheses concerning the cause of RGC death. Previously, glaucoma was defined by high intraocular pressure (IOP); during the past decade, however, glaucoma spec...... elucidating a possible role of low-grade inflammation as a causal factor in the pathogenesis of glaucoma....

  5. Role of eosinophilic airway inflammation in models of asthma

    Directory of Open Access Journals (Sweden)

    Lapa e Silva José R

    1997-01-01

    Full Text Available Eosinophils play a central role in the establishment and outcome of bronchial inflammation in asthma. Animal models of allergy are useful to answer questions related to mechanisms of allergic inflammation. We have used models of sensitized and boosted guinea pigs to investigate the nature of bronchial inflammation in allergic conditions. These animals develop marked bronchial infiltration composed mainly of CD4+ T-lymphocytes and eosinophils. Further provocation with antigen leads to degranulation of eosinophils and ulceration of the bronchial mucosa. Eosinophils are the first cells to increase in numbers in the mucosa after antigen challenge and depend on the expression of alpha 4 integrin to adhere to the vascular endothelium and transmigrate to the mucosa. Blockage of alpha4 integrin expression with specific antibody prevents not only the transmigration of eosinophils but also the development of bronchial hyperresponsiveness (BHR to agonists in sensitized and challenged animals, clearly suggesting a role for this cell type in this altered functional state. Moreover, introduction of antibody against Major Basic Protein into the airways also prevents the development of BHR in similar model. BHR can also be suppressed by the use of FK506, an immunosuppressor that reduces in almost 100% the infiltration of eosinophils into the bronchi of allergic animals. These data support the concept that eosinophil is the most important pro-inflammatory factor in bronchial inflammation associated with allergy.

  6. Can Skin Exposure to Sunlight Prevent Liver Inflammation?

    Directory of Open Access Journals (Sweden)

    Shelley Gorman

    2015-05-01

    Full Text Available Liver inflammation contributes towards the pathology of non-alcoholic fatty liver disease (NAFLD. Here we discuss how skin exposure to sunlight may suppress liver inflammation and the severity of NAFLD. Following exposure to sunlight-derived ultraviolet radiation (UVR, the skin releases anti-inflammatory mediators such as vitamin D and nitric oxide. Animal modeling studies suggest that exposure to UVR can prevent the development of NAFLD. Association studies also support a negative link between circulating 25-hydroxyvitamin D and NAFLD incidence or severity. Clinical trials are in their infancy and are yet to demonstrate a clear beneficial effect of vitamin D supplementation. There are a number of potentially interdependent mechanisms whereby vitamin D could dampen liver inflammation, by inhibiting hepatocyte apoptosis and liver fibrosis, modulating the gut microbiome and through altered production and transport of bile acids. While there has been a focus on vitamin D, other mediators induced by sun exposure, such as nitric oxide may also play important roles in curtailing liver inflammation.

  7. Hypothalamic inflammation: a double-edged sword to nutritional diseases

    Science.gov (United States)

    Cai, Dongsheng; Liu, Tiewen

    2015-01-01

    The hypothalamus is one of the master regulators of various physiological processes, including energy balance and nutrient metabolism. These regulatory functions are mediated by discrete hypothalamic regions that integrate metabolic sensing with neuroendocrine and neural controls of systemic physiology. Neurons and non-neuronal cells in these hypothalamic regions act supportively to execute metabolic regulations. Under conditions of brain and hypothalamic inflammation, which may result from overnutrition-induced intracellular stresses or disease-associated systemic inflammatory factors, extracellular and intracellular environments of hypothalamic cells are disrupted, leading to central metabolic dysregulations and various diseases. Recent research has begun to elucidate the effects of hypothalamic inflammation in causing diverse components of metabolic syndrome leading to diabetes and cardiovascular disease. These new understandings have provocatively expanded previous knowledge on the cachectic roles of brain inflammatory response in diseases, such as infections and cancers. This review describes the molecular and cellular characteristics of hypothalamic inflammation in metabolic syndrome and related diseases as opposed to cachectic diseases, and also discusses concepts and potential applications of inhibiting central/hypothalamic inflammation to treat nutritional diseases. PMID:22417140

  8. Effects of blueberries on inflammation, motor performance and cognitive function

    Science.gov (United States)

    Motor and cognitive function decrease with age, to include deficits in balance, coordination, gait, processing speed, executive function, memory, and spatial learning. These functional declines may be caused by long term increases in and susceptibility to oxidative stress and inflammation. Research ...

  9. Two-way interactions between inflammation and coagulation

    NARCIS (Netherlands)

    Levi, Marcel; van der Poll, Tom

    2005-01-01

    Activation of inflammatory and coagulation pathways is important in the pathogenesis of vascular disease. There is ample evidence that extensive cross-talk between these two systems exists, whereby inflammation not only leads to activation of coagulation, but coagulation also markedly affects

  10. Inflammation and the etiology of type 2 diabetes.

    Science.gov (United States)

    Sjöholm, Ake; Nyström, Thomas

    2006-01-01

    Type 2 diabetes is increasingly common worldwide and is beginning to strike younger age groups. Almost 90% of all patients with diabetes show insulin resistance, which also precedes the first symptoms of diabetes. The mechanisms underlying the development of insulin resistance are not well understood. In recent years, several studies have been published that implicate subclinical chronic inflammation as an important pathogenetic factor in the development of insulin resistance and type 2 diabetes. This opens new perspectives for diagnosis and treatment of early insulin resistance and incipient glucose intolerance. Surrogate markers for this low-grade chronic inflammation include CRP, IL-6 and TNF-alpha. Some antidiabetic agents, for example, glitazones that reduce insulin resistance, and insulin itself, reduce inflammation. Conversely, antiinflammatory drugs (ASA/NSAID) may improve glucose tolerance. Vasoactive drugs that are often prescribed to people with diabetes, for example, statins and ACE inhibitors/angiotensin receptor antagonists, also counteract inflammation and reduce the risk of type 2 diabetes. More specific and sensitive biomarkers should be identified, which may predict early disturbances in insulin sensitivity and cardiovascular risk. Also, inflammatory signalling pathways need to be explored in greater detail, and may form the basis of drugable targets against the epidemic of insulin resistance and atherosclerosis. Copyright (c) 2005 John Wiley & Sons, Ltd.

  11. STAT4 contributes to adipose tissue inflammation and atherosclerosis.

    Science.gov (United States)

    Dobrian, A D; Hatcher, M A; Brotman, J J; Galkina, E V; Taghavie-Moghadam, P; Pei, H; Haynes, B A; Nadler, J L

    2015-10-01

    Adipose tissue (AT) inflammation is an emerging factor contributing to cardiovascular disease. STAT4 is a transcription factor expressed in adipocytes and in immune cells and contributes to AT inflammation and insulin resistance in obesity. The objective of this study was to determine the effect of STAT4 deficiency on visceral and peri-aortic AT inflammation in a model of atherosclerosis without obesity. Stat4(-/-)Apoe(-/-) mice and Apoe(-/-) controls were kept either on chow or Western diet for 12 weeks. Visceral and peri-aortic AT were collected and analyzed for immune composition by flow cytometry and for cytokine/chemokine expression by real-time PCR. Stat4(-/-)Apoe(-/-) and Apoe(-/-) mice had similar body weight, plasma glucose, and lipids. Western diet significantly increased macrophage, CD4+, CD8+, and NK cells in peri-aortic and visceral fat in Apoe(-/-) mice. In contrast, in Stat4(-/-)Apoe(-/-) mice, a Western diet failed to increase the percentage of immune cells infiltrating the AT. Also, IL12p40, TNFa, CCL5, CXCL10, and CX3CL1 were significantly reduced in the peri-aortic fat in Stat4(-/-)Apoe(-/-) mice. Importantly, Stat4(-/-)Apoe(-/-) mice on a Western diet had significantly reduced plaque burden vs Apoe(-/-) controls. In conclusion, STAT4 deletion reduces inflammation in peri-vascular and visceral AT and this may contribute via direct or indirect effects to reduced atheroma formation. © 2015 Society for Endocrinology.

  12. Obesity and low-grade inflammation: a paediatric perspective.

    Science.gov (United States)

    Tam, C S; Clément, K; Baur, L A; Tordjman, J

    2010-02-01

    Childhood obesity is a major public health problem. Low-grade inflammation, a hallmark characterizing adult obesity, may be a pivotal mechanism linking obesity to its numerous systemic complications, with adipose tissue depots secreting and producing inflammatory mediators and visceral fat displaying an increased inflammatory profile. While knowledge is relatively scarce regarding the importance of the adipose tissue inflammation process in children, identifying its contribution in childhood obesity and the associated influences of age, sex, weight status, growth, and adipose depot phenotypes are crucial for understanding physiopathology and implementing early intervention strategies. We review the latest research linking obesity and inflammation in childhood focusing on serum inflammatory markers and the effectiveness of lifestyle interventions in improving systemic inflammation. Generally, there are significant correlations between body mass index and increased c-reactive protein and decreased adiponectin levels in children; these levels tend to be improved in interventions resulting in approximately 5% weight loss, regardless of the type or length of intervention. There is a need for further research measuring other inflammatory mediators (e.g. tumour necrosis factor (TNF)-alpha, IL-6, IL-8) and histological studies examining immune cell infiltration in adipose tissue depots in obese children.

  13. The Significance and Insignificance of Carbon Nanotube-Induced Inflammation

    Directory of Open Access Journals (Sweden)

    Matthew S.P. Boyles

    2014-02-01

    Full Text Available In the present review article immune responses induced by carbon nanotubes (CNTs are addressed. As inhalation is considered to be the primary entry route, and concern has been raised by similar high aspect ratio materials, the main focus lies on immune responses upon pulmonary exposure. Inflammation-related findings from both in vivo studies and in vitro models are reviewed, and the major responsible characteristics, which may drive CNT-induced inflammation in the lung, are discussed. In a second part, responses upon intentional administration of CNTs via subcutaneous and intravenous application are addressed, including their potential benefits and drawbacks for immunotherapy. Finally, the gastrointestinal tract as an alternative exposure route is briefly discussed. While there are many studies identifying numerous other factors involved in CNT-driven toxicity, e.g., cytotoxicity, oxidative stress, and genotoxicity, the focus of this review was kept solely on CNT-induced inflammation. Overall the literature has shown that CNTs are able to induce inflammation, which in some cases was a particularly robust response coinciding with the development of pro-fibrotic conditions. In the majority of cases the greatest inflammatory responses were associated with CNTs of considerable length and a high aspect ratio, accompanied by other factors like dispersion and sample purity.

  14. POSTNATAL INFLAMMATION IN THE PATHOGENESIS OF BRONCHOPULMONARY DYSPLASIA

    Science.gov (United States)

    Bhandari, Vineet

    2014-01-01

    Exposure to hyperoxia, invasive mechanical ventilation and systemic/local sepsis are important antecedents of postnatal inflammation in the pathogenesis of bronchopulmonary dysplasia (BPD). This review will summarize information obtained from animal (baboon, lamb/sheep, rat and mouse) models that pertain to the specific inflammatory agents and signaling molecules that predispose a premature infant to BPD. PMID:24578018

  15. The interaction between mesenchymal stem cells and steroids during inflammation.

    Science.gov (United States)

    Chen, X; Gan, Y; Li, W; Su, J; Zhang, Y; Huang, Y; Roberts, A I; Han, Y; Li, J; Wang, Y; Shi, Y

    2014-01-23

    Mesenchymal stem cells (MSCs) are believed to exert their regenerative effects through differentiation and modulation of inflammatory responses. However, the relationship between the severity of inflammation and stem cell-mediated tissue repair has not been formally investigated. In this study, we applied different concentrations of dexamethasone (Dex) to anti-CD3-activated splenocyte cultured with or without MSCs. As expected, Dex exhibited a classical dose-dependent inhibition of T-cell proliferation. Surprisingly, although MSCs also blocked T-cell proliferation, the presence of Dex unexpectedly showed a dose-dependent reversion of T-cell proliferation. This effect of Dex was found to be exerted through interfering STAT1 phosphorylation-prompted expression of inducible nitric oxide synthase (iNOS). Interestingly, inflammation-induced chemokines in MSCs was unaffected. To test the role of inflammation severity in stem cell-mediated tissue repair, we employed mice with carbon tetrachloride-induced advanced liver fibrosis and found that although MSCs alone were effective, concurrent administration of Dex abrogated the therapeutic effects of MSCs on fibrin deposition, serum levels of bilirubin, albumin, and aminotransferases, as well as T-lymphocyte infiltration, especially IFN-γ(+)CD4(+) and IL-17A(+)CD4(+)T cells. Likewise, iNOS(-/-) MSCs, which produce chemokines but not nitric oxide under inflammatory conditions, are ineffective in treating advanced liver fibrosis. Therefore, inflammation has a critical role in MSC-mediated tissue repair. In addition, concomitant application of MSCs with steroids should be avoided.

  16. Discovering new host-directed therapies to treat inflammation

    CSIR Research Space (South Africa)

    Fanucchi, Stephanie

    2017-08-01

    Full Text Available on immune genes that encode various inflammatory mediators (e.g. cytokines). Therefore, inflammation is controlled at the level of gene regulation – which can be described in simple terms as the ability of genes to be switched on and off. This is a highly...

  17. Inflammation and cardiac dysfunction during sepsis, muscular dystrophy, and myocarditis

    Directory of Open Access Journals (Sweden)

    Ying Li

    2013-12-01

    Full Text Available Inflammation plays an important role in cardiac dysfunction under different situations. Acute systemic inflammation occurring in patients with severe burns, trauma, and inflammatory diseases causes cardiac dysfunction, which is one of the leading causes of mortality in these patients. Acute sepsis decreases cardiac contractility and impairs myocardial compliance. Chronic inflammation such as that occurring in Duchenne muscular dystropshy and myocarditis may cause adverse cardiac remodeling including myocyte hypertrophy and death, fibrosis, and altered myocyte function. However, the underlying cellular and molecular mechanisms for inflammatory cardiomyopathy are still controversial probably due to multiple factors involved. Potential mechanisms include the change in circulating blood volume; a direct inhibition of myocyte contractility by cytokines (tumor necrosis factor (TNF-a, interleukin (IL-1b; abnormal nitric oxide and reactive oxygen species (ROS signaling; mitochondrial dysfunction; abnormal excitation-contraction coupling; and reduced calcium sensitivity at the myofibrillar level and blunted b-adrenergic signaling. This review will summarize recent advances in diagnostic technology, mechanisms, and potential therapeutic strategies for inflammation-induced cardiac dysfunction.

  18. Inflammation aggravates disease severity in Marfan syndrome patients.

    NARCIS (Netherlands)

    Radonic, T.; Witte, P. de; Groenink, M.; Waard, V. de; Lutter, R.; Eijk, M. van; Jansen, J.L.M.; Timmermans, J.; Kempers, M.J.; Scholte, A.J.H.A.; Hilhorst-Hofstee, Y.; Berg, M.P van den; Tintelen, J.P. van; Pals, G.; Baars, M.J.; Mulder, B.J.; Zwinderman, A.H.

    2012-01-01

    BACKGROUND: Marfan syndrome (MFS) is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-beta signaling. However, the contribution of tissue inflammation is not

  19. Inflammation Aggravates Disease Severity in Marfan Syndrome Patients

    NARCIS (Netherlands)

    Radonic, Teodora; de Witte, Piet; Groenink, Maarten; de Waard, Vivian; Lutter, Rene; van Eijk, Marco; Jansen, Marnix; Timmermans, Janneke; Kempers, Marlies; Scholte, Arthur J.; Hilhorst-Hofstee, Yvonne; van den Berg, Maarten P.; van Tintelen, J. Peter; Pals, Gerard; Baars, Marieke J. H.; Mulder, Barbara J. M.; Zwinderman, Aeilko H.

    2012-01-01

    Background: Marfan syndrome (MFS) is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-beta signaling. However, the contribution of tissue inflammation is not

  20. Ethylene, an early marker of systemic inflammation in humans

    NARCIS (Netherlands)

    Paardekooper, L.M.; Bogaart, G. van den; Kox, M.; Dingjan, I.; Neerincx, A.H.; Bendix, M.B.; Beest, M.T.; Harren, F.J.M; Risby, T.; Pickkers, P.; Marczin, N.; Cristescu, S.M.

    2017-01-01

    Ethylene is a major plant hormone mediating developmental processes and stress responses to stimuli such as infection. We show here that ethylene is also produced during systemic inflammation in humans and is released in exhaled breath. Traces of ethylene were detected by laser spectroscopy both in

  1. Regulating Damage from Sterile Inflammation: A Tale of Two Tolerances.

    Science.gov (United States)

    Wu, Shin-Rong; Reddy, Pavan

    2017-04-01

    The severity of immunopathology from non-infectious inflammation is mainly understood and is managed by targeting immune cells. However, the role of target tissues in determining damage severity has been largely overlooked. Here, we discuss the concept of 'tissue tolerance' for tissue-intrinsic programs that ameliorate organ damage in the setting of sterile immunopathology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Obesity, Inflammation, and Lung Injury (OILI: The Good

    Directory of Open Access Journals (Sweden)

    Cheryl Wang

    2014-01-01

    Full Text Available Obesity becomes pandemic, predisposing these individuals to great risk for lung injury. In this review, we focused on the anti-inflammatories and addressed the following aspects: adipocytokines and obesity, inflammation and other mechanisms, adipocytokines and lung injury in obesity bridged by inflammation, and potential therapeutic targets. To sum up, the majority of evidence supported that adiponectin, omentin, and secreted frizzled-related protein 5 (SFRP5 were reduced significantly in obesity, which is associated with increased inflammation, indicated by increase of TNFα and IL-6, through activation of toll-like receptor (TLR4 and nuclear factor light chain κB (NF-κB signaling pathways. Administration of these adipocytokines promotes weight loss and reduces inflammation. Zinc-α2-glycoprotein (ZAG, vaspin, IL-10, interleukin-1 receptor antagonist (IL-1RA, transforming growth factor β (TGF-β1, and growth differentiation factor 15 (GDF15 are also regarded as anti-inflammatories. There were controversial reports. Furthermore, there is a huge lack of studies for obesity related lung injury. The effects of adiponectin on lung transplantation, asthma, chronic obstructive pulmonary diseases (COPD, and pneumonia were anti-inflammatory and protective in lung injury. Administration of IL-10 agonist reduces mortality of acute lung injury in rabbits with acute necrotizing pancreatitis, possibly through inhibiting proinflammation and strengthening host immunity. Very limited information is available for other adipocytokines.

  3. Ghrelin receptor regulates adipose tissue inflammation in aging

    Science.gov (United States)

    Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth ho...

  4. [Menstruation, inflammation and comorbidities: implications for woman health].

    Science.gov (United States)

    Graziottin, A; Zanello, P P

    2015-02-01

    Menstruation is the genital sign of systemic endocrine events. Heterogeneity of perimenstrual symptoms is associated with levels of inflammation, triggered by the fall of estrogens at genital and systemic level. Aim of the review is to concisely analyze the evidence on: 1) genital and systemic endocrine and inflammatory events associated with periods and perimenstrual symptoms; 2) rationale of intervention to reduce their intensity and impact on women's lives. This review of the literature, selected with a clinical perspective, supports the inflammatory basis of the menstrual event, triggered by the estrogens' and progesterone' fall. Moreover, the review analyzes the endocrine and inflammatory basis of perimenstrual pelvic and extrapelvic symptoms such as: menstrual pain, menstrual irregularities, premenstrual syndrome, gastrointestinal symptoms, catamenial headache, depression, perimenstrual myalgia, joint pain, allergies and asthma, heavy menstrual bleeding, associated ironless anemia, brain and behavioral consequences. Inflammation, with increase of cytokines and other markers, is modulated by the degranulation of mast cells at the basal level of the endometrium, in the blood, in all the organs where mast-cell are already activated from local pathologies and within the brain. The shift of inflammation from physiological to a pathologic intensity increases the severity of perimenstrual symptoms. Symptoms persist, moderately attenuated, also during the hormone free interval (HFI) in contraception. The HFI reduction from seven to two days significantly reduces menstrual inflammation and associated symptoms.

  5. Targeting inflammation with autoantigen-specific T cells

    NARCIS (Netherlands)

    Guichelaar, T.

    2008-01-01

    Chronic autoimmune diseases are driven by cells that respond to tissue components of the body. Inflammation in diseases like rheumatoid arthritis, diabetes or multiple sclerosis, can be suppressed by drug therapy. However, the broad range of immunosuppressive action of these drugs often does not

  6. Cancer and inflammation studies using zebrafish cell lines

    NARCIS (Netherlands)

    He, Shuning

    2010-01-01

    As the zebrafish, Danio rerio, has been increasingly used as an animal model for biomedical research, we aimed to establish zebrafish cell line models for inflammation and cancer studies in this thesis. Several zebrafish cell lines were characterized and their genetic and physiological properties

  7. Obesity, inflammation, and lung injury (OILI): the good.

    Science.gov (United States)

    Wang, Cheryl

    2014-01-01

    Obesity becomes pandemic, predisposing these individuals to great risk for lung injury. In this review, we focused on the anti-inflammatories and addressed the following aspects: adipocytokines and obesity, inflammation and other mechanisms, adipocytokines and lung injury in obesity bridged by inflammation, and potential therapeutic targets. To sum up, the majority of evidence supported that adiponectin, omentin, and secreted frizzled-related protein 5 (SFRP5) were reduced significantly in obesity, which is associated with increased inflammation, indicated by increase of TNF α and IL-6, through activation of toll-like receptor (TLR4) and nuclear factor light chain κ B (NF- κ B) signaling pathways. Administration of these adipocytokines promotes weight loss and reduces inflammation. Zinc-α 2-glycoprotein (ZAG), vaspin, IL-10, interleukin-1 receptor antagonist (IL-1RA), transforming growth factor β (TGF-β1), and growth differentiation factor 15 (GDF15) are also regarded as anti-inflammatories. There were controversial reports. Furthermore, there is a huge lack of studies for obesity related lung injury. The effects of adiponectin on lung transplantation, asthma, chronic obstructive pulmonary diseases (COPD), and pneumonia were anti-inflammatory and protective in lung injury. Administration of IL-10 agonist reduces mortality of acute lung injury in rabbits with acute necrotizing pancreatitis, possibly through inhibiting proinflammation and strengthening host immunity. Very limited information is available for other adipocytokines.

  8. Cannabinoids mediate opposing effects on inflammation-induced intestinal permeability

    Science.gov (United States)

    Alhamoruni, A; Wright, KL; Larvin, M; O'Sullivan, SE

    2012-01-01

    BACKGROUND AND PURPOSE Activation of cannabinoid receptors decreases emesis, inflammation, gastric acid secretion and intestinal motility. The ability to modulate intestinal permeability in inflammation may be important in therapy aimed at maintaining epithelial barrier integrity. The aim of the present study was to determine whether cannabinoids modulate the increased permeability associated with inflammation in vitro. EXPERIMENTAL APPROACH Confluent Caco-2 cell monolayers were treated for 24 h with IFNγ and TNFα (10 ng·mL−1). Monolayer permeability was measured using transepithelial electrical resistance and flux measurements. Cannabinoids were applied either apically or basolaterally after inflammation was established. Potential mechanisms of action were investigated using antagonists for CB1, CB2, TRPV1, PPARγ and PPARα. A role for the endocannabinoid system was established using inhibitors of the synthesis and degradation of endocannabinoids. KEY RESULTS Δ9-Tetrahydrocannabinol (THC) and cannabidiol accelerated the recovery from cytokine-induced increased permeability; an effect sensitive to CB1 receptor antagonism. Anandamide and 2-arachidonylglycerol further increased permeability in the presence of cytokines; this effect was also sensitive to CB1 antagonism. No role for the CB2 receptor was identified in these studies. Co-application of THC, cannabidiol or a CB1 antagonist with the cytokines ameliorated their effect on permeability. Inhibiting the breakdown of endocannabinoids worsened, whereas inhibiting the synthesis of endocannabinoids attenuated, the increased permeability associated with inflammation. CONCLUSIONS AND IMPLICATIONS These findings suggest that locally produced endocannabinoids, acting via CB1 receptors play a role in mediating changes in permeability with inflammation, and that phytocannabinoids have therapeutic potential for reversing the disordered intestinal permeability associated with inflammation. LINKED ARTICLES This

  9. PET imaging of acute and chronic inflammation in living mice

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Qizhen; Cai, Weibo; Li, Zi-Bo; Chen, Kai; He, Lina; Chen, Xiaoyuan [Stanford University School of Medicine, The Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford, CA (United States); Li, Hui-Cheng; Hui, Mizhou [AmProtein Corporation, Camarillo, CA (United States)

    2007-11-15

    In this study, we evaluated the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced acute and chronic inflammation in living mice by PET imaging of TNF-{alpha} and integrin {alpha}{sub v}{beta}{sub 3} expression. TPA was topically applied to the right ear of BALB/c mice every other day to create the inflammation model. {sup 64}Cu-DOTA-etanercept and {sup 64}Cu-DOTA-E{l_brace}E[c(RGDyK)]{sub 2}{r_brace}{sub 2} were used for PET imaging of TNF-{alpha} and integrin {alpha}{sub v}{beta}{sub 3} expression in both acute and chronic inflammation. Hematoxylin and eosin staining, ex vivo autoradiography, direct tissue sampling, and immunofluorescence staining were also performed to confirm the non-invasive PET imaging results. The ear thickness increased significantly and the TNF-{alpha} level more than tripled after a single TPA challenge. MicroPET imaging using {sup 64}Cu-DOTA-etanercept revealed high activity accumulation in the inflamed ear, reaching 11.1 {+-} 1.3, 13.0 {+-} 2.0, 10.9 {+-} 1.4, 10.2 {+-} 2.2%ID/g at 1, 4, 16, and 24 h post injection, respectively (n = 3). Repeated TPA challenges caused TPA-specific chronic inflammation and reduced {sup 64}Cu-DOTA-etanercept uptake due to lowered TNF-{alpha} expression. {sup 64}Cu-DOTA-E{l_brace}E[c(RGDyK)]{sub 2}{r_brace}{sub 2} uptake in the chronically inflamed ears (after four and eight TPA challenges) was significantly higher than in the control ears and those after one TPA challenge. Immunofluorescence staining revealed increased integrin {beta}{sub 3} expression, consistent with the non-invasive PET imaging results using {sup 64}Cu-DOTA-E{l_brace}E[c(RGDyK)]{sub 2}{r_brace}{sub 2} as an integrin {alpha}{sub v} {beta}{sub 3}-specific radiotracer. Biodistribution and autoradiography studies further confirmed the quantification capability of microPET imaging. Successful PET imaging of TNF- {alpha} expression in acute inflammation and integrin {alpha}{sub v} {beta}{sub 3} expression in chronic inflammation provides

  10. Effects of TLC-Ag dressings on skin inflammation.

    Science.gov (United States)

    Bisson, Jean-François; Hidalgo-Lucas, Sophie; Bouschbacher, Marielle; Thomassin, Laetitia

    2013-06-01

    The TLC-Ag dressings, a combination of technology lipido-colloid and silver salts, are used to promote healing in wounds with risks or signs of local infection, thanks to the antimicrobial properties of the silver salts. Nanocrystalline silver dressings containing nanocrystalline silver, also used to improve wound healing, present both antimicrobial and anti-inflammatory effects. The aim of this study was to investigate the anti-inflammatory effects of TLC-Ag dressings in a model of chronic skin inflammation induced by repeated application of 12-O-tetradecanoylphorbol-13-acetate to the skin of hairless mice, in comparison with TLC dressing, Silcryst nanocrystalline dressing, desonide cream 0.05%, a corticoid cream used as positive control, and gauze. Daily treatments of the mice began 7 days after the start of induction of chronic skin inflammation and lasted for 7 days. A macroscopic score was performed daily during the treatment period until the mice killing on day 15 and skin samples were taken for histopathological analysis. TLC-Ag reduced significantly the macroscopic score of chronic skin inflammation from day 10 in comparison with gauze and TLC dressing, similarly to Silcryst nanocrystalline dressing and desonide cream, which presented the best anti-inflammatory effects. No significant differences were observed between TLC dressing and gauze. TLC-Ag reduced significantly the microscopic score of chronic skin inflammation in comparison with TLC dressing and gauze, similarly to Silcryst nanocrystalline dressing but significantly less than desonide cream. These results demonstrate that TLC-Ag dressings present significant anti-inflammatory effects on chronic skin inflammation. They can improve wound healing, due to both the antimicrobial and anti-inflammatory properties. © 2013 Japanese Dermatological Association.

  11. Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations.

    Directory of Open Access Journals (Sweden)

    Edith T Zemanick

    Full Text Available Pulmonary exacerbations (PEx, frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF. Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood.To determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx.Expectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0-3d. and late treatment (>7d. for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE; and circulating C-reactive protein (CRP were measured.Thirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA of Pseudomonas (r = -0.67, p<0.001, decreased FEV(1% predicted (r = 0.49, p = 0.03 and increased CRP (r = -0.58, p = 0.01. In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV₁. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV₁ response to treatment than Pseudomonas or Staphylococcus.Anaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens.

  12. TRPA1 mediates mechanical sensitization in nociceptors during inflammation.

    Directory of Open Access Journals (Sweden)

    Richard C Lennertz

    Full Text Available Inflammation is a part of the body's natural response to tissue injury which initiates the healing process. Unfortunately, inflammation is frequently painful and leads to hypersensitivity to mechanical stimuli, which is difficult to treat clinically. While it is well established that altered sensory processing in the spinal cord contributes to mechanical hypersensitivity (central sensitization, it is still debated whether primary afferent neurons become sensitized to mechanical stimuli after tissue inflammation. We induced inflammation in C57BL/6 mice via intraplantar injection of Complete Freund's Adjuvant. Cutaneous C fibers exhibited increased action potential firing to suprathreshold mechanical stimuli. We found that abnormal responses to intense mechanical stimuli were completely suppressed by acute incubation of the receptive terminals with the TRPA1 inhibitor, HC-030031. Further, elevated responses were predominantly exhibited by a specific subgroup of C fibers, which we determined to be C-Mechano Cold sensitive fibers. Thus, in the presence of HC-030031, C fiber mechanical responses in inflamed mice were not different than responses in saline-injected controls. We also demonstrate that injection of the HC-030031 compound into the hind paw of inflamed mice alleviates behavioral mechanical hyperalgesia without affecting heat hyperalgesia. Further, we pharmacologically anesthetized the TRPA1-expressing fibers in vivo by co-injecting the membrane-impermeable sodium channel inhibitor QX-314 and the TRPA1 agonist cinnamaldehyde into the hind paw. This approach also alleviated behavioral mechanical hyperalgesia in inflamed mice but left heat hypersensitivity intact. Our findings indicate that C-Mechano Cold sensitive fibers exhibit enhanced firing to suprathreshold mechanical stimuli in a TRPA1-dependent manner during inflammation, and that input from these fibers drives mechanical hyperalgesia in inflamed mice.

  13. Inflammation in Parkinson’s disease: Role of glucocorticoids

    Directory of Open Access Journals (Sweden)

    Maria Trinidad eHerrero

    2015-04-01

    Full Text Available Chronic inflammation is a major characteristic feature of Parkinson’s disease (PD. Studies in PDpatients show evidence of augmented levels of potent pro-inflammatory molecules e.g. TNF-α, iNOS,IL-1β whereas in experimental Parkinsonism it has been consistently demonstrated that dopaminergicneurons are particularly vulnerable to activated glia releasing these toxic factors. Recent geneticstudies point to the role of immune system in the etiology of PD, thus in combination withenvironmental factors, both peripheral and CNS-mediated immune responses could play importantroles in onset and progression of PD. Whereas microglia, astrocytes and infiltrating T cells are knownto mediate chronic inflammation, the roles of other immune-competent cells are less well understood.Inflammation is a tightly controlled process. One major effector system of regulation is HPA axis.Glucocorticoids released from adrenal glands upon stimulation of HPA axis, in response to either cellinjury or presence of pathogen, activate their receptor, GR. GR regulates inflammation both throughdirect transcriptional action on target genes and by indirectly inhibiting transcriptional activities oftranscriptional factors such as NF-kB, AP-1 or interferon regulatory factors. In PD patients, the HPAaxis is unbalanced and the cortisol levels are significantly increased, implying a deregulation of GRfunction in immune cells. In experimental Parkinsonism, the activation of microglial GR has a crucialeffect in diminishing microglial cell activation and reducing dopaminergic degeneration. Moreover,glucocorticoids are also known to regulate human brain vasculature as well as blood brain barrierpermeability, any dysfunction in their actions may influence infiltration of cytotoxic moleculesresulting in increased vulnerability of dopamine neurons in PD. Overall, deregulation ofGR actions is likely important in dopamine neuron degeneration throughestablishment of chronic inflammation.

  14. Attenuation of congenital portosystemic shunt reduces inflammation in dogs.

    Science.gov (United States)

    Tivers, Michael S; Handel, Ian; Gow, Adam G; Lipscomb, Victoria J; Jalan, Rajiv; Mellanby, Richard J

    2015-01-01

    Liver disease is a major cause of morbidity and mortality. One of the most significant complications in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incompletely understood, which has resulted in the development of a wide range of experimental models. Congenital portosystemic shunt is one of the most common congenital disorders diagnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiology of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a congenital portosystemic shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a congenital portosystemic shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil, lymphocyte and monocyte concentrations together with C-reactive protein concentrations, would decrease following successful treatment of congenital portosystemic shunts in dogs. One hundred and forty dogs with a congenital portosystemic shunt were enrolled into the study. We found that the proportion of dogs with a monocyte concentration above the reference range was significantly greater in dogs with hepatic encephalopathy at time of initial diagnosis. Importantly, neutrophil and monocyte concentrations significantly decreased following surgical congenital portosystemic shunt attenuation. We also found a significant decrease in C-reactive protein concentrations following surgical attenuation of congenital portosystemic shunts. Our study demonstrates that

  15. Melatonin reduces changes to small intestinal microvasculature during systemic inflammation.

    Science.gov (United States)

    Lansink, Maren Oude; Patyk, Vivien; de Groot, Herbert; Effenberger-Neidnicht, Katharina

    2017-05-01

    Systemic inflammation is known to impair the microcirculation in intestine and other organs as a result of multifactorial events. Here, we show that melatonin selectively reduces changes to the small intestinal microvasculature during systemic inflammation. Lipopolysaccharide (LPS) was infused at a rate of 0.5 mg/kg × h to induce systemic inflammation in male Wistar rats. Melatonin (single dose: 3 mg/kg × 15 min) was intravenously administered before as well as 120 and 240 min after the beginning of the LPS infusion. Systemic parameters were determined in regular intervals. Small intestine, liver, and kidney were histologically (structure of the microvessels, intravascular blood accumulation, and hemorrhages) and immunohistochemically (mast cells, granulocytes, and macrophages) analyzed. Continuous infusion of LPS resulted in dilated microvessels with intravascular blood accumulation (congestion) in liver and small intestine, the latter being particularly pronounced. Blood vessel walls remained intact, there were no hemorrhages. Melatonin significantly reduced these changes to the microvasculature in small intestine, but not in liver. It further reduced mast cell and granulocytes count in small intestine enhanced by LPS. However, except for the systemic blood pressure, melatonin neither improved LPS-dependent changes to systemic parameters nor mortality. Changes to the microvasculature during systemic inflammation are most pronounced in small intestine. Melatonin selectively diminishes these changes to small intestinal microvasculature, probably by reducing the local immune cells recruitment. However, changes to the small intestine are not decisive for the survival. We assume that the therapeutic benefit of melatonin is more likely in local intestinal inflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Systemic inflammation and lung function: A longitudinal analysis.

    Science.gov (United States)

    Hancox, Robert J; Gray, Andrew R; Sears, Malcolm R; Poulton, Richie

    2016-02-01

    Systemic inflammation is associated with impaired lung function in healthy adults as well as in patients with lung disease. The mechanism for this association is unknown and it is unclear if systemic inflammation leads to impaired lung function or if poor lung function leads to inflammation. We explored the temporal associations between blood C-reactive protein (CRP), fibrinogen, and white blood cells, and lung function in young adults. Spirometry, plethysmography, and diffusion capacity were measured in a population-based cohort at ages 32 and 38 years. High-sensitivity CRP, fibrinogen, and white blood cells were measured at the same ages. Higher levels of CRP and, to a lesser extent, fibrinogen were associated with lower lung volumes in cross-sectional analyses at both ages 32 and 38 years. Higher CRP and fibrinogen at age 32 were associated with higher FEV1 and FEV1/FVC at age 38, but not other measures of lung function. Lower lung volumes (total lung capacity, functional residual capacity, and residual volume) but not airflow obstruction (FEV1/FVC) at age 32 were associated with higher CRP at age 38. Associations between age 32 lung function and fibrinogen at follow-up were weaker, but consistent. There were no longitudinal associations between white blood cells and lung function. We found no evidence that systemic inflammation causes a decline in lung function. However, lower lung volumes were associated with higher CRP and fibrinogen at follow-up indicating that pulmonary restriction may be a risk factor for systemic inflammation. The mechanism for this association remains unclear. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Translational Systems Approaches to the Biology of Inflammation and Healing

    Science.gov (United States)

    Vodovotz, Yoram; Constantine, Gregory; Faeder, James; Mi, Qi; Rubin, Jonathan; Bartels, John; Sarkar, Joydeep; Squires, Robert H.; Okonkwo, David O.; Gerlach, Jörg; Zamora, Ruben; Luckhart, Shirley; Ermentrout, Bard; An, Gary

    2011-01-01

    Inflammation is a complex, non-linear process central to many of the diseases that affect both developed and emerging nations. A systems-based understanding of inflammation, coupled to translational applications, is therefore necessary for efficient development of drugs and devices, for streamlining analyses at the level of populations, and for the implementation of personalized medicine. We have carried out an iterative and ongoing program of literature analysis, generation of prospective data, data analysis, and computational modeling in various experimental and clinical inflammatory disease settings. These simulations have been used to gain basic insights into the inflammatory response under baseline, gene-knockout, and drug-treated experimental animals for in silico studies associated with the clinical settings of sepsis, trauma, acute liver failure, and wound healing to create patient-specific simulations in polytrauma, traumatic brain injury, and vocal fold inflammation; and to gain insight into host-pathogen interactions in malaria, necrotizing enterocolitis, and sepsis. These simulations have converged with other systems biology approaches (e.g., functional genomics) to aid in the design of new drugs or devices geared towards modulating inflammation. Since they include both circulating and tissue-level inflammatory mediators, these simulations transcend typical cytokine networks by associating inflammatory processes with tissue/organ impacts via tissue damage/dysfunction. This framework has now allowed us to suggest how to modulate acute inflammation in a rational, individually optimized fashion. This plethora of computational and intertwined experimental/engineering approaches is the cornerstone of Translational Systems Biology approaches for inflammatory diseases. PMID:20170421

  18. Affective reactivity to daily stressors is associated with elevated inflammation.

    Science.gov (United States)

    Sin, Nancy L; Graham-Engeland, Jennifer E; Ong, Anthony D; Almeida, David M

    2015-12-01

    Inflammation increases the risk of chronic diseases, but the links between emotional responses to daily events and inflammation are unknown. We examined individual differences in affective reactivity to daily stressors (i.e., changes in positive and negative affect in response to stressors) as predictors of inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP). A cross-sectional sample of 872 adults from the National Study of Daily Experiences (substudy of Midlife in the United States II) reported daily stressors and affect during telephone interviews for 8 days. Blood samples were obtained at a separate clinic visit and assayed for inflammatory markers. Multilevel models estimated trait affective reactivity slopes for each participant, which were inputted into regression models to predict inflammation. People who experienced greater decreases in positive affect on days when stressors occurred (i.e., positive affect reactivity) had elevated log IL-6, independent of demographic, physical, psychological, and behavioral factors (B = 1.12, SE = 0.45, p = .01). Heightened negative affect reactivity was associated with higher log CRP among women (p = .03) but not men (p = .57); health behaviors accounted for this association in women. Adults who fail to maintain positive affect when faced with minor stressors in everyday life appear to have elevated levels of IL-6, a marker of inflammation. Women who experience increased negative affect when faced with minor stressors may be at particular risk of elevated inflammation. These findings add to growing evidence regarding the health implications of affective reactivity to daily stressors. (c) 2015 APA, all rights reserved).

  19. Dietary patterns, insulin sensitivity and inflammation in older adults.

    Science.gov (United States)

    Anderson, A L; Harris, T B; Tylavsky, F A; Perry, S E; Houston, D K; Lee, J S; Kanaya, A M; Sahyoun, N R

    2012-01-01

    Several studies have linked dietary patterns to insulin sensitivity and systemic inflammation, which affect risk of multiple chronic diseases. The purpose of this study was to investigate the dietary patterns of a cohort of older adults, and to examine relationships of dietary patterns with markers of insulin sensitivity and systemic inflammation. The Health, Aging and Body Composition (Health ABC) Study is a prospective cohort study of 3075 older adults. In Health ABC, multiple indicators of glucose metabolism and systemic inflammation were assessed. Food intake was estimated with a modified Block food frequency questionnaire. In this study, dietary patterns of 1751 participants with complete data were derived by cluster analysis. Six clusters were identified, including a 'healthy foods' cluster, characterized by higher intake of low-fat dairy products, fruit, whole grains, poultry, fish and vegetables. In the main analysis, the 'healthy foods' cluster had significantly lower fasting insulin and homeostasis model assessment of insulin resistance values than the 'breakfast cereal' and 'high-fat dairy products' clusters, and lower fasting glucose than the 'high-fat dairy products' cluster (P≤0.05). No differences were found in 2-h glucose. With respect to inflammation, the 'healthy foods' cluster had lower interleukin-6 than the 'sweets and desserts' and 'high-fat dairy products' clusters, and no differences were seen in C-reactive protein or tumor necrosis factor-α. A dietary pattern high in low-fat dairy products, fruit, whole grains, poultry, fish and vegetables may be associated with greater insulin sensitivity and lower systemic inflammation in older adults.

  20. Significance of coexistent granulomatous inflammation and lung cancer.

    Science.gov (United States)

    Dagaonkar, Rucha S; Choong, Caroline V; Asmat, Atasha Binti; Ahmed, Dokeu Basheer A; Chopra, Akhil; Lim, Albert Y H; Tai, Dessmon Y H; Kor, Ai Ching; Goh, Soon Keng; Abisheganaden, John; Verma, Akash

    2017-04-01

    Coexistence of lung cancer and granulomatous inflammation in the same patient confuses clinicians. We aimed to document the prevalence, clinicopathological features, treatment outcomes and prognosis in patients with coexisting granulomatous inflammation undergoing curative lung resection for lung cancer, in a tuberculosis (TB)-endemic country. An observational cohort study of patients with lung cancer undergoing curative resection between 2012 and 2015 in a tertiary centre in Singapore. One hundred and twenty-seven patients underwent lung resection for cancer, out of which 19 (14.9%) had coexistent granulomatous inflammation in the resected specimen. Median age was 68 years and 58.2% were males. Overall median (range) survival was 451 (22-2452) days. Eighteen (14%) patients died at median duration of 271 days after surgery. The postsurgery median survival for those alive was 494 (29-2452) days in the whole group. Subgroup analysis did not reveal any differences in age, gender, location of cancer, radiological features, type of cancer, chemotherapy, history of TB or survival in patients with or without coexistent granulomatous inflammation. Incidental detection of granulomatous inflammation in patients undergoing lung resection for cancer, even in a TB-endemic country, may not require any intervention. Such findings may be due to either mycobacterial infection in the past or 'sarcoid reaction' to cancer. Although all patients should have their resected specimen sent for acid-fast bacilli culture and followed up until the culture results are reported, the initiation of the management of such patients as per existing lung cancer management guidelines does not affect their outcome adversely. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  1. Attenuation of congenital portosystemic shunt reduces inflammation in dogs.

    Directory of Open Access Journals (Sweden)

    Michael S Tivers

    Full Text Available Liver disease is a major cause of morbidity and mortality. One of the most significant complications in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incompletely understood, which has resulted in the development of a wide range of experimental models. Congenital portosystemic shunt is one of the most common congenital disorders diagnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiology of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a congenital portosystemic shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a congenital portosystemic shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil, lymphocyte and monocyte concentrations together with C-reactive protein concentrations, would decrease following successful treatment of congenital portosystemic shunts in dogs. One hundred and forty dogs with a congenital portosystemic shunt were enrolled into the study. We found that the proportion of dogs with a monocyte concentration above the reference range was significantly greater in dogs with hepatic encephalopathy at time of initial diagnosis. Importantly, neutrophil and monocyte concentrations significantly decreased following surgical congenital portosystemic shunt attenuation. We also found a significant decrease in C-reactive protein concentrations following surgical attenuation of congenital portosystemic shunts. Our study

  2. Creatine kinase activity in dogs with experimentally induced acute inflammation

    Directory of Open Access Journals (Sweden)

    Dimitrinka Zapryanova

    2013-01-01

    Full Text Available The main purpose of this study was to investigate the effect of acute inflammation on total creatine kinase (CK activity in dogs. In these animals, CK is an enzyme found predominantly in skeletal muscle and significantly elevated serum activity is largely associated with muscle damage. Plasma increases in dogs are associated with cell membrane leakage and will therefore be seen in any condition associated with muscular inflammation. The study was induced in 15 mongrel male dogs (n=9 in experimental group and n=6 in control group at the age of two years and body weight 12-15 kg. The inflammation was reproduced by inoculation of 2 ml turpentine oil subcutaneously in lumbar region. The plasma activity of creatine kinase was evaluated at 0, 6, 24, 48, 72 hours after inoculation and on days 7, 14 and 21 by a kit from Hospitex Diagnostics. In the experimental group, the plasma concentrations of the CK-activity were increased at the 48th hour (97.48±6.92 U/L and remained significantly higher (p<0.05 at the 72 hour (97.43±2.93 U/L compared to the control group (77.08±5.27 U/L. The results of this study suggest that the evaluation of creatine kinase in dogs with experimentally induced acute inflammation has a limited diagnostic value. It was observed that the creatine kinase activity is slightly affected by the experimentally induced acute inflammation in dogs.

  3. Expression Profiles of Inflammation-associated microRNAs in Periapical Lesions and Human Periodontal Ligament Fibroblasts Inflammation.

    Science.gov (United States)

    Yue, Junli; Song, Dongzhe; Lu, Wanlu; Lu, Ying; Zhou, Wei; Tan, Xuelian; Zhang, Lan; Huang, Dingming

    2016-12-01

    microRNAs (miRNAs) have been identified to be closely related to inflammatory diseases. The aim of our study was to identify expression profiles of miRNAs associated with inflammation in apical periodontitis (AP) lesions and human periodontal ligament fibroblasts (HPDLFs) inflammation. Total RNAs were extracted from 10 AP lesions, 6 control tissues, and HPDLFs using lysis buffer. Expressions of miRNAs (miR-29b, 106b, 125b, 143, 155, and 198) were detected by real-time polymerase chain reaction. The dual luciferase assay was used to test miR-155 directly targeted semaphorein3a (SEMA3A). Western Blot and the enzyme-linked immunosorbent assay were used to detect the protein expressions of SEMA3A and proinflammatory cytokines, respectively. All experiments were repeated at least 3 times. Data were analyzed using the independent sample t test. The previously mentioned miRNAs were all significantly up-regulated in AP lesions (P  .05). Overexpression of miR-155 induced proinflammatory phenotype, and down-regulation reduced the other miRNAs in HPDLFs (P acute HPDLFs inflammation and down-regulated (decreased) in AP lesions (P lesions and HPDLFs inflammation were different. miR-155 may play a crucial role in apical periodontitis progression by directly inhibiting SEMA3A. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  4. Age-Related Macular Degeneration in the Aspect of Chronic Low-Grade Inflammation (Pathophysiological ParaInflammation

    Directory of Open Access Journals (Sweden)

    Małgorzata Nita

    2014-01-01

    Full Text Available The products of oxidative stress trigger chronic low-grade inflammation (pathophysiological parainflammation process in AMD patients. In early AMD, soft drusen contain many mediators of chronic low-grade inflammation such as C-reactive protein, adducts of the carboxyethylpyrrole protein, immunoglobulins, and acute phase molecules, as well as the complement-related proteins C3a, C5a, C5, C5b-9, CFH, CD35, and CD46. The complement system, mainly alternative pathway, mediates chronic autologous pathophysiological parainflammation in dry and exudative AMD, especially in the Y402H gene polymorphism, which causes hypofunction/lack of the protective complement factor H (CFH and facilitates chronic inflammation mediated by C-reactive protein (CRP. Microglial activation induces photoreceptor cells injury and leads to the development of dry AMD. Many autoantibodies (antibodies against alpha beta crystallin, alpha-actinin, amyloid, C1q, chondroitin, collagen I, collagen III, collagen IV, elastin, fibronectin, heparan sulfate, histone H2A, histone H2B, hyaluronic acid, laminin, proteoglycan, vimentin, vitronectin, and aldolase C and pyruvate kinase M2 and overexpression of Fcc receptors play role in immune-mediated inflammation in AMD patients and in animal model. Macrophages infiltration of retinal/choroidal interface acts as protective factor in early AMD (M2 phenotype macrophages; however it acts as proinflammatory and proangiogenic factor in advanced AMD (M1 and M2 phenotype macrophages.

  5. The impact of ruxolitinib treatment on inflammation-mediated comorbidities in myelofibrosis and related neoplasms

    DEFF Research Database (Denmark)

    Bjørn, Mads Emil; Hasselbalch, Hans Carl

    2015-01-01

    The inflammation-mediated comorbidities in myelofibrosis (MF) and related neoplasms (MPNs) likely reflect the concurrent immune deregulation and systemic inflammatory nature of the MPNs, emphasizing the link between chronic systemic inflammation, immune deregulation, and the malignant clone. JAK1...

  6. Capsaicin-induced neurogenic inflammation in the skin in patients with symptoms induced by odorous chemicals

    DEFF Research Database (Denmark)

    Holst, Helle; Arendt-Nielsen, Lars; Mosbech, Holger

    2011-01-01

    Intradermal injection of capsaicin induces the axonal release of neuropeptides, vasodilatation and flare, e.g. neurogenic inflammation. The spatial profile of neurogenic inflammation in the skin has been studied in various experimental models. Polarization spectroscopy imaging introduced recently...

  7. A Zinc Chelator TPEN Attenuates Airway Hyperresponsiveness Airway Inflammation in Mice In Vivo

    Directory of Open Access Journals (Sweden)

    Satoru Fukuyama

    2011-01-01

    Conclusions: In pulmonary allergic inflammation induced in mice immunized with antigen without alum, zinc chelator inhibits airway inflammation and hyperresponsiveness. These findings suggest that zinc may be a therapeutic target of allergic asthma.

  8. NF-kappa B Activation is Required for the Transition of Pulmonary Inflammation to Muscle Atrophy

    NARCIS (Netherlands)

    Langen, Ramon C. J.; Haegens, Astrid; Vernooy, Juanita H. J.; Wouters, Emiel F. M.; de Winther, Menno P. J.; Carlsen, Harald; Steele, Chad; Shoelson, Steven E.; Schols, Annemie M. W. J.

    2012-01-01

    Rationale Disease exacerbations and muscle wasting are negative prognostic factors of COPD. Transient systemic inflammation and malnutrition have been implicated in skeletal muscle wasting following acute exacerbations of COPD. However, the interaction between systemic inflammation and malnutrition

  9. Genetic Polymorphisms in Genes Involved in Inflammation and Prostate Cancer Risk

    National Research Council Canada - National Science Library

    Salinas, Claudia A

    2008-01-01

    ...), and elevated markers of inflammation, such as interleukin-6. Prior literature suggests that cancer risk increases in the presence of chronic injury to tissues, as can result from chronic inflammation...

  10. BET bromodomain proteins and epigenetic regulation of inflammation: implications for type 2 diabetes and breast cancer.

    Science.gov (United States)

    Nicholas, Dequina A; Andrieu, Guillaume; Strissel, Katherine J; Nikolajczyk, Barbara S; Denis, Gerald V

    2017-01-01

    Chronic inflammation drives pathologies associated with type 2 diabetes (T2D) and breast cancer. Obesity-driven inflammation may explain increased risk and mortality of breast cancer with T2D reported in the epidemiology literature. Therapeutic approaches to target inflammation in both T2D and cancer have so far fallen short of the expected improvements in disease pathogenesis or outcomes. The targeting of epigenetic regulators of cytokine transcription and cytokine signaling offers one promising, untapped approach to treating diseases driven by inflammation. Recent work has deeply implicated the Bromodomain and Extra-Terminal domain (BET) proteins, which are acetylated histone "readers", in epigenetic regulation of inflammation. This review focuses on inflammation associated with T2D and breast cancer, and the possibility of targeting BET proteins as an approach to regulating inflammation in the clinic. Understanding inflammation in the context of BET protein regulation may provide a basis for designing promising therapeutics for T2D and breast cancer.

  11. Associations of low grade inflammation and endothelial dysfunction with depression : The Maastricht study

    NARCIS (Netherlands)

    van Dooren, F.E.P.; Schram, M.T.; Schalkwijk, C.G.; Stehouwer, C.D.; Henry, R.M.; Dagnelie, P.C.; Schaper, N.C.; van der Kallen, C. J.; Koster, A.; Sep, S. J.; Denollet, J.; Verhey, F.R.J.; Pouwer, F.

    2016-01-01

    Background The pathogenesis of depression may involve low-grade inflammation and endothelial dysfunction. We aimed to evaluate the independent associations of inflammation and endothelial dysfunction with depressive symptoms and depressive disorder, and the role of lifestyle factors in this

  12. Molecular Ultrasound Imaging for the Detection of Neural Inflammation

    Science.gov (United States)

    Volz, Kevin R.

    Molecular imaging is a form of nanotechnology that enables the noninvasive examination of biological processes in vivo. Radiopharmaceutical agents are used to selectively target biochemical markers, which permits their detection and evaluation. Early visualization of molecular variations indicative of pathophysiological processes can aid in patient diagnoses and management decisions. Molecular imaging is performed by introducing molecular probes into the body. Molecular probes are often contrast agents that have been nanoengineered to selectively target and tether to molecules, enabling their radiologic identification. Ultrasound contrast agents have been demonstrated as an effective method of detecting perfusion at the tissue level. Through a nanoengineering process, ultrasound contrast agents can be targeted to specific molecules, thereby extending ultrasound's capabilities from the tissue to molecular level. Molecular ultrasound, or targeted contrast enhanced ultrasound (TCEUS), has recently emerged as a popular molecular imaging technique due to its ability to provide real-time anatomical and functional information in the absence of ionizing radiation. However, molecular ultrasound represents a novel form of molecular imaging, and consequently remains largely preclinical. A review of the TCEUS literature revealed multiple preclinical studies demonstrating its success in detecting inflammation in a variety of tissues. Although, a gap was identified in the existing evidence, as TCEUS effectiveness for detection of neural inflammation in the spinal cord was unable to be uncovered. This gap in knowledge, coupled with the profound impacts that this TCEUS application could have clinically, provided rationale for its exploration, and use as contributory evidence for the molecular ultrasound body of literature. An animal model that underwent a contusive spinal cord injury was used to establish preclinical evidence of TCEUS to detect neural inflammation. Imaging was

  13. Cholesterol-Induced Hepatic Inflammation Does Not Underlie the Predisposition to Insulin Resistance in Dyslipidemic Female LDL Receptor Knockout Mice

    NARCIS (Netherlands)

    Gruben, Nanda; Funke, Anouk; Kloosterhuis, Niels J.; Schreurs, Marijke; Sheedfar, Fareeba; Havinga, Rick; Houten, Sander M.; Shiri-Sverdlov, Ronit; van de Sluis, Bart; Kuivenhoven, Jan Albert; Koonen, Debby P. Y.; Hofker, Marten H.

    2015-01-01

    Chronic inflammation is considered a causal risk factor predisposing to insulin resistance. However, evidence is accumulating that inflammation confined to the liver may not be causal to metabolic dysfunction. To investigate this, we assessed if hepatic inflammation explains the predisposition

  14. The Core Mechanism of Dry Eye Disease (DED) Is Inflammation

    Science.gov (United States)

    Wei, Yi; Asbell, Penny A.

    2014-01-01

    Purpose The purpose of this article is to review the evidence for the hypothesis that the core mechanism of Dry Eye Disease (DED) is inflammation, including evidence from recent basic, clinical and translational research involving human patients, animal models, and cell cultures. Method Using the key words “dry eye + inflammation” , the authors conducted a comprehensive search of the PubMed and Web of Science databases for scientific articles published in English between January 1st 1900 and August 30th 2013 on the role of inflammation in DED in cell cultures, animal models and humans. The resulting articles were then categorized and reviewed. Results The literature search revealed a total of 458 publications, almost all published after 1992. The percentages of original studies and review articles are 77.29% (354) and 22.71% (104), respectively. Among the original studies, the number of reports on inflammation of human DED is 200 (43.7%); animal models, 115 (25.1 %); and cell cultures, 39 (8.5 %). The human DED studies reveal changes of numerous inflammatory cells and mediators in ocular surface and tear film and those changes can be attenuated or reversed by anti-inflammatory drug treatments. The animal DED studies demonstrate that DED is likely a dominant T-lymphocytes, especially T-helper 17-subset (Th17)-mediated autoimmune disease and that the autoimmune-driven inflammatory cycles are fundamentally linked with DED progression. These results are mirrored and confirmed by a number of corneal and conjunctival epithelial cell culture studies that clearly demonstrate an inflammatory immune response pattern when those cells are exposed to desiccation, inflammatory mediators or high osmolarity shock. A yearly distributing plot revealed that 76% were published from 2003 to 2011, 53% from 2008 to 2012, and 11% during the first 9 months of 2013. This distribution signifies a rapidly growing awareness of the importance of inflammation in DED pathogenesis. Conclusion

  15. Inflammation, Autophagy, and Obesity: Common Features in the Pathogenesis of Pancreatitis and Pancreatic Cancer

    OpenAIRE

    Gukovsky, Ilya; Li, Ning; Todoric, Jelena; Gukovskaya, Anna; Karin, Michael

    2013-01-01

    Inflammation and autophagy are cellular defense mechanisms. When these processes are deregulated (deficient or overactivated) they produce pathologic effects, such as oxidative stress, metabolic impairments, and cell death. Unresolved inflammation and disrupted regulation of autophagy are common features of pancreatitis and pancreatic cancer. Furthermore, obesity, a risk factor for pancreatitis and pancreatic cancer, promotes inflammation and inhibits or deregulates autophagy, creating an env...

  16. No overall damage progression despite persistent inflammation in adalimumab-treated psoriatic arthritis patients

    DEFF Research Database (Denmark)

    Poggenborg, René Panduro; Wiell, Charlotte; Bøyesen, Pernille

    2014-01-01

    of inflammation remained present (week 48 total inflammation score median = 9). Several DCE-MRI parameters also decreased (P correlated (ρ = 0.62) with conventional MRI total inflammation score. No statistically significant changes in bone erosion or proliferation scores were observed. With CT...... to subsequent erosive progression detected by CT. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov/, NCT01465438....

  17. DMPD: Acetylation of MKP-1 and the control of inflammation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18922786 Acetylation of MKP-1 and the control of inflammation. Chi H, Flavell RA. S...ci Signal. 2008 Oct 14;1(41):pe44. (.png) (.svg) (.html) (.csml) Show Acetylation of MKP-1 and the control of inflammation.... PubmedID 18922786 Title Acetylation of MKP-1 and the control of inflammation. Authors Chi H,

  18. DMPD: Fragments of extracellular matrix as mediators of inflammation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18243041 Fragments of extracellular matrix as mediators of inflammation. Adair-Kirk...l) Show Fragments of extracellular matrix as mediators of inflammation. PubmedID 18243041 Title Fragments of... extracellular matrix as mediators of inflammation. Authors Adair-Kirk TL, Senior

  19. A rare case of orbital granulomatous inflammation from explosive hydraulic oil masquerading as orbital cellulitis.

    Science.gov (United States)

    Cheema, Marvi; Roelofs, Kelsey; Jivraj, Imran; West, Robert; Rasmussen, Steve; Chan, Audrey

    2017-10-20

    The differential diagnosis for acute orbital inflammation is broad. We report a case of granulomatous orbital inflammation due to high-pressure oil injury to the orbit presenting as an atypical orbital cellulitis. Here we review the presentation and treatment of orbital inflammation from oil.

  20. Depression and immunity: Inflammation and depressive symptoms in multiple sclerosis

    Science.gov (United States)

    Gold, Stefan M.; Irwin, Michael R.

    2013-01-01

    An increasing body of evidence suggests that patients with major depressive disorder show alterations in immunological markers including increases in proinflammatory cytokine activity and inflammation. Animal models of a depression-like syndrome called sickness behavior have clearly shown that cytokines are implicated in the development of these symptoms. Inflammation of the CNS is a pathological hallmark of multiple sclerosis (MS). Patients affected by this disease also show a high incidence of depression. In light of accumulating evidence for cytokine-mediated sickness behavior from animal studies, it is possible that some aspects of depression and fatigue in multiple sclerosis may be linked to inflammatory markers. Here, we review the current knowledge in the field and illustrate how the sickness behavior model may be applied to investigate depressive symptoms in inflammatory neurological diseases such as multiple sclerosis. PMID:19389584