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)

Interleukin-1 (IL-1) is a 17-kDa pro-inflammatory cytokine synthesized from a variety of cell types primarily in association with disease states or during host perturbation such as immune responses. At pM or even fM concentrations, IL-1 triggers various responses in nearly all cells. It appears that there is little or no major role for IL-1 in homoeostatic mechanisms. There are two IL-1's (alpha and beta) each with its distinct sequence; there are two IL-1 receptors. Disease states such as local and systemic infection, septic shock, degenerative arthritis and autoimmune diseases such as nephritis, vasculitis and inflammatory bowel disease appear to be mediated, in part, by IL-1. Organ failure, capillary leak and death occur in animals after a combination of tumour necrosis factor (TNF) and IL-1 which is more effective in inducing these changes than either cytokine alone. IL-1 is also a potent inducer of endothelial cell adhesion molecules, IL-6, and IL-8, a neutrophil chemotactic and activating factor. Strategies for reducing the effects of IL-1 have been based on suppression of transcription, translation, or secretion; more recently, receptor blockade has been a new approach. A naturally occurring IL-1-specific receptor antagonist (IL-1ra), which shares 40% conserved amino-acid homology with IL-1 beta, binds to IL-1 surface receptors with the same affinity as IL-1 but does not possess agonist activity and acts as a competitive inhibitor of IL-1. Studies using the IL-1ra to block endogenous IL-1 in a variety of animal disease models suggest that IL-1 plays a key role in triggering the cascade of inflammatory responses. In addition, the IL-1ra reduces the spontaneous production of growth factors and proliferation of leukaemic cells. The IL-1ra may be an advantageous therapy in patients with sepsis, diabetes, inflammatory bowel, arthritis and cancer.
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PMID:Reduction of inflammation by decreasing production of interleukin-1 or by specific receptor antagonism. 139 23

Reactional states in leprosy are produced by different immunologic mechanisms and are responsible for a major component of tissue damage of the disease. Reversal reactions exhibit increased CD4 T cell infiltration in lesions and augmented cell-mediated immune reactivity to Ag of Mycobacterium leprae that can rapidly produce nerve damage. Erythema nodosum leprosum (ENL) reactions also have CD4 T cell infiltration but appear to be associated with the formation of immune complexes that are responsible for panniculitis, arthritis, vasculitis, and nerve injury. Because these reactional states may serve as paradigms for other types of human immunologically mediated tissue damage, this study sought to characterize the dynamic changes in cytokines associated with these reactions. Expression of cytokine mRNA in lesions of leprosy reactional states were measured by PCR. In reversal reactions, IL-1 beta, TNF-alpha, IL-2, and IFN-gamma mRNA were prominent and found to increase during the reaction, concomitant with decreases in expression of mRNA for IL-4, IL-5, and IL-10. In ENL, selective increases in the expression of IL-6, IL-8, and IL-10 mRNA was observed, with persistent expression of IL-4 and IL-5 mRNA. Reversal reactions represent naturally occurring delayed-type hypersensitivity reactions that favor macrophage activation and protective immunity, but which can engender concomitant cell injury. In contrast, ENL lesions represent immediate-type hypersensitivity reactions reflecting the selective stimulation of cytokines that attract neutrophils, stimulate antibody production, and down-regulate macrophage activation. The analysis of cytokine dynamics within different inflammatory responses can provide insights into immune mechanisms of tissue damage, and provide a useful framework for developing strategies for therapeutic intervention.
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PMID:Cytokine patterns of immunologically mediated tissue damage. 150 Jul 26

The present study was undertaken to determine the anti-neutrophil cytoplasmic antibody (ANCA) levels in 96 patients with various collagen diseases associated with renal vasculitis and vasculitic syndrome in Japan. The results indicated that cytoplasmic(C)-ANCA is an autoantibody highly specific to Wegener's granulomatosis (WG) and that it is also active in renal injury. The relationships between ANCA and focal segmental necrotizing GN, i.e., renal vasculitis as proposed by Balow, were investigated. Perinuclear(P)-ANCA was detected with high sensitivity and specificity in renal vasculitis without WG, and the severity of necrotizing and crescentic nephritis in WG was correlated especially well with the C-ANCA titer. Detection of ANCA is considered clinically useful for the etiological differentiation of renal vasculitis, suggesting the possibility that C-ANCA may be involved in the onset of vasculitis of the glomerular capillary vessels in WG. The presence of C-ANCA and cytokines (IL-1 beta and TNF-alpha) is important in the pathogenesis of vasculitis and GN in WG.
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PMID:Clinical significance of anti-neutrophil cytoplasmic antibodies (ANCA) in collagen diseases associated with vasculitic syndrome in Japan. 163 82

Cytokines are known to alter a number of vascular tissue cell functions. The aim of this retrospective study was to determine serum cytokine levels in patients with vasculitis and to analyse the possible relation to the severity of the disease. Tumour necrosis factor alpha (TNF alpha), interleukin-1 (IL-1)beta, IL-2, interferon (IFN)- and IFN-gamma were assayed in 33 patients with polyarteritis nodosa (PAN) or Churg and Strauss angiitis (CSA), and three with Wegener granulomatosis (WG). Serum cytokine changes were observed in most patients with active disease, i.e. before treatment was started. In the majority of patients with PAN or CSA, there was a marked increase in serum IFN-alpha and IL-2 levels, while TNF-alpha and IL-beta levels were moderately elevated. Serum IFN-gamma remained undetectable in all but one of these patients. In patients with WG, serum IFN-alpha and IL-2 levels were also elevated, whereas IL-1 beta, IFN-gamma and TNF alpha levels remained within normal limits. In paired samples of patients with PAN, IFN-alpha and IL-2 levels were significantly higher before than after treatment. These preliminary data suggest that a particular pattern of cytokine changes is associated with vasculitis and that cytokines might be involved in the pathogenesis of PAN/CSA and WG. Prospective studies are warranted to determine whether cytokines could be considered for the monitoring of disease activity and therapy.
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PMID:Serum cytokine changes in systemic vasculitis. 247 51

The authors have investigated the effects of cytokines and lipopolysaccharide (LPS) on mRNA levels of c-sis (platelet-derived growth factor (PDGF)-B chain), PDGF-A chain, and interleukin 1 beta (IL-1 beta) genes in human vascular endothelial cells (EC). IL-1, tumor necrosis factor (TNF), and LPS not only enhanced the accumulation of c-sis mRNA, but also induced IL-1 beta gene expression. Interferon-gamma (IFN-gamma), in contrast, suppressed the accumulation of c-sis mRNA profoundly and PDGF-A chain mRNA to a lesser extent. The cytokine, in addition, suppressed the release of PDGF-like proteins by EC, while maintaining the growth of EC. IFN-gamma, however, augmented the levels of IL-1 beta mRNA in cultured EC in association with LPS or IL-1, suggesting that the suppression of c-sis expression was not mediated through modulation of IL-1 gene expression by IFN-gamma. These results raise the possibility that IFN-gamma may play a novel regulatory role in the pathogenesis of vascular diseases such as atherosclerosis and vasculitis.
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PMID:Interferon-gamma modulates messenger RNA levels of c-sis (PDGF-B chain), PDGF-A chain, and IL-1 beta genes in human vascular endothelial cells. 249 3

Interleukin-1 (IL-1) mediates many components of generalized host response to injury and may also contribute to local vascular pathology during immune or inflammatory responses. Because altered function of smooth muscle cells (SMC) accompanies certain vascular diseases, we tested whether SMC themselves might produce this hormone. Unstimulated SMC contain little or no IL-1 mRNA. However, exposure to bacterial endotoxin caused accumulation of IL-1 mRNA in SMC cultured from human vessels. Endotoxin maximally increased IL-1 beta mRNA in SMC after 4-6 h. The lowest effective concentration of endotoxin was 10 pg/ml. 10 ng/ml produced maximal increases in IL-1 beta mRNA. Interleukin-1 alpha mRNA was detected when SMC were incubated with endotoxin under "superinduction" conditions with cycloheximide. Endotoxin-stimulated SMC also released biologically functional IL-1, measured as thymocyte costimulation activity inhibitable by anti-IL-1 antibody. Thus, human SMC can express IL-1 beta and IL-1 alpha genes, or very similar ones, and secrete biologically active product in response to a pathological stimulus. Endogenous local production of this inflammatory mediator by the blood vessel wall's major cell type could play an important early role in the pathogenesis of vasculitis and arteriosclerosis.
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PMID:Inducible interleukin-1 gene expression in human vascular smooth muscle cells. 349 Oct 91

Interleukin 1 (IL-1) alters several potentially pathogenic endothelial cell (EC) functions. The authors report here that recombinant human IL-1 (rIL-1) alpha (0.1 to 10 ng/ml) or IL-1-beta (1 to 100 ng/ml) induce concentration- and time-dependent increases in IL-1-beta mRNA levels in EC derived from adult human saphenous vein. rIL-1 induced IL-1-alpha mRNA only in EC treated concomitantly with cycloheximide (2 micrograms/ml). IL-1-beta mRNA production began within 1 hr of exposure to rIL-1, peaked after 24 hr, and declined thereafter. Actinomycin D prevented the appearance of IL-1 mRNA in rIL-1-treated EC. rIL-1 also induced the release of biologically active IL-1 from EC, which was inhibited by cycloheximide (1 microgram/ml). When compared on the basis of their activity in the thymocyte costimulation assay, rIL-1-alpha and rIL-1-beta were equipotent as inducers of IL-1 production by EC. EC stimulated with rIL-1 produced prostaglandin E2, which inhibits IL-1 production by other cell types and also decreases the responsiveness of thymocytes to IL-1. When EC were exposed to rIL-1 in the presence of indomethacin (1 microgram/ml), which blocked prostaglandin E2 production, greater amounts of rIL-1-induced IL-1 release were detected, although the inhibitor did not affect IL-1-beta mRNA levels. IL-1-induced IL-1 production was unlikely to be caused by endotoxin contamination of tissue culture media or IL-1 preparations, because the lipopolysaccharide (LPS) antagonist polymyxin B (10 micrograms/ml) blocked LPS-induced IL-1 production by EC but did not affect IL-1 release in response to rIL-1-beta (100 ng/ml). The IL-1-inducing property of rIL-1-beta was heat-labile, whereas heated LPS stimulated EC IL-1 production. The source of IL-1 in our cultures was not monocyte/macrophages, as treatment of EC with monoclonal antibody to the monocyte antigen Mo2 under conditions that lysed adherent peripheral blood monocytes did not affect production of IL-1 by EC in response to LPS (1 microgram/ml) or rIL-1-beta (100 ng/ml). IL-1 elicits a coordinated program of altered endothelial function that increases adhesiveness for leukocytes and coagulability. IL-1-induced IL-1 gene expression in human adult EC could thus provide a positive feedback mechanism in the pathogenesis of vascular disease including atherosclerosis, vasculitis, and allograft rejection.
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PMID:Interleukin 1 induces interleukin 1. II. Recombinant human interleukin 1 induces interleukin 1 production by adult human vascular endothelial cells. 349 83

Interleukin 1 (IL-1) can induce potentially pathogenic functions of vascular endothelial cells. This mediator was formerly thought to be produced primarily by activated macrophages. We report here that bacterial endotoxin and recombinant human tumor necrosis factor cause accumulation of IL-1 beta mRNA in adult human vascular endothelial cells. IL-1 alpha mRNA was also detected when endothelial cells were exposed to endotoxin under "superinduction" conditions in the presence of cycloheximide. Metabolic labeling of these cells during endotoxin stimulation demonstrated increased synthesis and secretion of immunoprecipitable IL-1 protein that comigrated electrophoretically with the predominant monocyte species. In parallel with increased IL-1 mRNA and protein, endothelial cells exposed to endotoxin also release biologically active IL-1 that was neutralized by anti-IL-1-antibody. Because bloodborne agents must traverse the endothelium before entering tissues, endothelial IL-1 production induced by microbial products or other injurious stimuli could initiate local responses to invasion. Endothelial cells are both a source of and target for IL-1; accordingly, this novel autocrine mechanism might play an early role in the pathogenesis of vasculitis, allograft rejection, and arteriosclerosis.
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PMID:Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells. 352 9

Intravenous infusion of particulate yeast cell wall glucan into rats results in the synchronous development of angiocentric pulmonary granulomas that are composed almost entirely of monocytes and macrophages. Previous studies indicate that locally produced monocyte chemoattractant protein-1 (MCP-1) is required for full granuloma development. Because tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 (IL-1) can induce MCP-1 production in a variety of cell types, we sought to determine their potential regulatory roles in this model. A single infusion of anti-TNF-alpha antibody at the time of glucan infusion (time 0) markedly reduced MCP-1 mRNA levels at 1 and 6 hours but not at later time points; there was no effect on granuloma size or number measured at 48 hours. When multiple infusions of anti-TNF-alpha antibody were administered over a 23-hour period (0 to 23 hours), MCP-1 mRNA was reduced through 24 hours, there was a significant reduction in peak bronchoalveolar lavage fluid MCP-1 activity at 48 hours, and there were marked reductions in granuloma size and number at 48 hours. Similar results were observed in animals that received infusions of anti-IL-1 beta. Infusion of anti-IL-1 beta at time 0 resulted in moderate reductions in MCP-1 mRNA at 1 and 6 hours and had no effect on granuloma size or number measured at 48 hours. When multiple infusions of anti-IL-1 beta were administered over a 23-hour period (0 to 23 hours), MCP-1 mRNA was reduced through 24 hours, there was a moderate reduction in peak bronchoalveolar lavage fluid MCP-1 activity at 48 hours, and there were marked reductions in granuloma size and number at 48 hours. A single infusion of anti-TNF-alpha and anti-IL-1 beta together at time 0 resulted in marked reductions in whole lung MCP-1 and mRNA at 1 and 6 hours, but not at 24 hours. Multiple combined infusions of anti-TNF-alpha and anti-IL-1 beta over a 23-hour period resulted in additive reductions in MCP-1 mRNA through 24 hours, bronchoalveolar lavage fluid MCP-1 activity at 48 hours, and granuloma size and number at 48 hours. These data suggest that locally produced TNF-alpha and IL-1 beta play regulatory roles in glucan-induced pulmonary granulomatous vasculitis through the modulation of local MCP-1 production.
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PMID:Regulatory roles of tumor necrosis factor-alpha and interleukin-1 beta in monocyte chemoattractant protein-1-mediated pulmonary granuloma formation in the rat. 785 54

Humoral and cellular immune mechanisms are thought to be involved in various forms of vasculitis and glomerulonephritis. Recent clinical and experimental results point to a role of cytokines in ANCA-positive vasculitides. In patients with malignant rheumatoid arthritis (MRA) which is characteristically induced by vasculitis in extra-articular lesions, serum soluble IL-2 receptor level was significantly higher than in rheumatoid arthritis patients without vasculitis. In Wegener's granulomatosis, TNF-alpha, IL-1 beta and IL-2 receptor positive infiltrating cells were observed in the kidneys of these patients, and in these patients, plasma levels of TNF-alpha and soluble IL-2 receptor were markedly increased. These results suggest that in ANCA-positive vasculitis TNF-alpha and IL-1 beta are produced in situ by activated infiltrating mononuclear cells and resident renal cells. In patients with giant cell arteritis and Kawasaki disease, increased levels of leukaemic inhibitory factor (LIF) and TNF-alpha were observed, respectively. These inflammatory cytokines increased in the vascular tissues and circulation may be a result of increased production by infiltrated cells or vascular cells such as endothelial cells or may be a result of endothelial cell lysis.
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PMID:[Cytokines and vasculitis]. 793 78


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