Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, compelling evidence has accumulated that inflammation results from a cascade of events that are orchestrated by cytokines. Cytokines are products of nonimmune and immune cells which regulate the recruitment, differentiation, and proliferation of inflammatory cells. Although there is redundancy in cytokine production and function, major pathways of cytokines have been identified. Besides macrophages, T cells represent important sources of pro- and anti-inflammatory cytokines. In support of a critical regulatory role of T cells in inflammation, two T cell subtypes characterized by different cytokine profiles have been described. TH1 cells produce interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and are prone to interact with macrophages. TH2 cells are producers of IL-4, IL-5, and IL-10 and are capable of supporting B cells and eosinophils. Here, we are providing evidence that different human inflammatory diseases are characterized by distinct in situ cytokine patterns. Giant cell vasculitis represents a typical TH1-like disease, whereas TH2 helper cells appear to be more important in rheumatoid arthritis. Given the association of different diseases with cytokine profiles, the question arises how the microenvironment influences cytokine pattern and thus disease and whether mediators produced at the site of inflammation could serve as therapeutic targets to modulate the cytokine cascade. Prostaglandin E(2) (PGE(2)) is an important inflammatory mediator. We have examined the influence of PGE(2) and the PGE analog misoprostol on T-cell function and T-cell cytokine production. Here, we describe that IL-2 and IFN-gamma production are sensitive to PGE(2) and misoprostol, whereas IL-4 and IL-5 are unaffected. Thus, in the presence of PGE(2), TH0 cells acquire a TH2-like function, whereas TH1-like aspects are suppressed. We suggest that PGE(2) and misoprostol might represent useful modulators of the cytokine network.
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PMID:T-Cell Derived Lymphokines as Regulators of Chronic Inflammation: Potential Targets for Immunomodulation? 1185 80

The aim of this study was to elucidate the characteristics, pathogenesis and treatment strategy of hypertrophic pachymeningitis that is associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA). We retrospectively investigated clinical, radiological, immunological and pathological profiles of 36 patients with immune-mediated or idiopathic hypertrophic pachymeningitis, including 17 patients with myeloperoxidase-ANCA, four patients with proteinase 3-ANCA, six patients with other immune-mediated disorders, and nine patients with 'idiopathic' variety. Myeloperoxidase-ANCA-positive hypertrophic pachymeningitis was characterized by: (i) an elderly female predominance; (ii) 82% of patients diagnosed with granulomatosis with polyangiitis (previously known as Wegener's granulomatosis) according to Watts' algorithm; (iii) a high frequency of patients with lesions limited to the dura mater and upper airways, developing headaches, chronic sinusitis, otitis media or mastoiditis; (iv) a low frequency of patients with the 'classical or generalized form' of granulomatosis with polyangiitis involving the entire upper and lower airways and kidney, or progressing to generalized disease, in contrast to proteinase 3-ANCA-positive hypertrophic pachymeningitis; (v) less severe neurological damage according to the modified Rankin Scale and low disease activity according to the Birmingham Vasculitis Activity Score compared with proteinase 3-ANCA-positive hypertrophic pachymeningitis; (vi) increased levels of CXCL10, CXCL8 and interleukin 6 in cerebrospinal fluids, and increased numbers of T cells, neutrophils, eosinophils, plasma cells and monocytes/macrophages in autopsied or biopsied dura mater with pachymeningitis, suggesting TH1-predominant granulomatous lesions in hypertrophic pachymeningitis, as previously reported in pulmonary or renal lesions of granulomatosis with polyangiitis; and (vii) greater efficacy of combination therapy with prednisolone and cyclophosphamide compared with monotherapy with prednisolone. Proteinase 3-ANCA may be considered a marker for more severe neurological damage, higher disease activity and a higher frequency of the generalized form compared with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. However, categorization into 'granulomatosis with polyangiitis' according to Watts' algorithm and immunological or pathological features were common in both proteinase 3- and myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. These data indicate that most patients with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis should be categorized as having the central nervous system-limited form of ANCA-associated vasculitis, consistent with the concept of ophthalmic-, pulmonary- or renal-limited vasculitis.
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PMID:Hypertrophic pachymeningitis: significance of myeloperoxidase anti-neutrophil cytoplasmic antibody. 2427 23