1,721,016 research outputs found

    Autoinflammatory diseases: How to put the fire inside the body out?

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    Autoinflammatory diseases (AIDs) are a group of distinct hereditable disorders characterized by unexplained, recurrent episodes of fever and severe inflammation, most commonly involving skin, joints, gut, and eyes. Mutations in inflammasome-related proteins, particularly in NOD-like receptor (NLR) genes, have been strongly associated to the occurrence of AIDs. However, new genes and dysfunctional proteins have recently been identified and the spectrum of AIDs is ever-expanding. In fact, it has been suggested to encompass among AIDs other disorders which share some clinical features, but are not clearly familial, or are not characterized by fever as a prominent symptom, or are polygenic. In this issue of Autoimmunity Reviews some novel and burning aspects of AIDs were covered and the relationship between AIDs and autoimmune diseases was discussed

    Cytokine levels in human synovial fluid during the different stages of acute gout: role of transforming growth factor β1 in the resolution phase.

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    Abstract OBJECTIVES: To determine the most relevant parameters in synovial fluid (SF) during the various stages of acute gout. METHODS: SFs from 38 gouty patients were analysed for white blood cell (WBC) count, percentage of polymorphonuclear cells (PMNs) and levels of interleukin 1β (IL-1β), IL-6, IL-8, tumour necrosis factorα (TNFα) and transforming growth factor β1 (TGFβ1). Patients were divided into three groups according to the length of time since onset of the attack: phase I (0-48 h), phase II (days 3-4) and phase III (days 5-7). RESULTS: Levels of WBCs were similar in SFs from phases I and II, while phase III showed the lowest WBC count. Percentages of PMNs were raised in all SFs. None of the cytokines analysed differed between phases I and II except for TGFβ1, which was higher in phase II. IL-1β, IL-6 and TNFα were higher in group 1 than in group 3. Levels of all the cytokines assessed, with the exception of TGFβ1, were significantly lower in phase III than in phase II IL-1β, p<0.05; IL-6, p<0.01; IL-8, p<0.001; TNFα, p<0.05).TGFβ1 levels were highest in SFs from phase III. CONCLUSION: Cytokine levels in SFs may change depending on the different stages of acute gout, highlighting the role of TGFβ1 in the resolution of gout

    HDL inhibit cytokine production in a mouse model of urate crystal-induced inflammation

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    Abstract OBJECTIVES: To evaluate whether high density lipoproteins (HDL) affect monosodium urate (MSU) crystal-induced inflammation in the murine air pouch model. METHODS: MSU crystals were prepared by Denko's method and sterilized by heating at 180°C for 2 h before each experiment. Human HDL were isolated from peripheral blood of healthy volunteers. MSU crystals (2 mg in 1 ml of PBS) were injected into subcutaneous air pouches in mice in the presence or absence of HDL (0.1 mg). Negative control pouches received 1 ml of PBS. To recover pouch fluid, the pouches were washed with 2 ml of PBS after the animals were sacrificed. The leukocyte count in the lavage fluids was obtained using a hemocytometer and differential leukocyte count was determined by May-Grunwald-Giemsa staining. IL-6, KC, CCL2 and TNF-α levels were measured in exudates by ELISA. RESULTS: MSU crystals increased the number of leukocytes and the neutrophil migration, as well as the concentrations of IL-6, KC and CCL2 in pouch fluids, while the TNF-α levels were not detectable. The treatment with HDL led to a reduction in all inflammatory parameters: the leukocyte count decreased by 73%; the neutrophil density decreased by 35%; the IL-6, KC and CCL2 concentration decreased by 4-, 6- and 5-fold respectively. CONCLUSIONS: This study shows that HDL may limit the inflammatory process by inhibiting leukocyte recruitment and cytokine release. HDL are likely to represent a mechanism of control of crystal-induced inflammation
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