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)

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

We recently identified a syndrome of recurrent cutaneous eosinophilic vasculitis in three patients. These patients had in common widespread pruritic, erythematous, purpuric papules and angioedema of face and hands associated with peripheral blood eosinophilia. Eight skin biopsies from these three patients all showed necrotizing vasculitis of the small vessels of the skin, with exclusively eosinophilic infiltration and minimal or no leukocytoclasis. The disease followed a chronic course, with recurrent, itchy, swelling skin lesions and without evidence of systemic involvement over observation periods of 3, 17, and 23 years. The skin lesions responded promptly to systemic steroid treatment, but two patients required maintenance doses for control of the disease. Immunofluorescence studies showed marked deposition of the cytotoxic eosinophil granule major basic protein in the affected vessel walls. Eosinophil-active cytokine IL-5 was detected in the serum of one patient. Expression of the vascular cell adhesion molecule-1 for eosinophil adherence was detected on the endothelium of the affected vessels. Because this disease showed distinctive clinical manifestations and characteristic histopathological features, we believe it is a distinct entity and should be distinguished from other types of vasculitis.
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PMID:Eosinophilic vasculitis syndrome: recurrent cutaneous eosinophilic necrotizing vasculitis. 764 Jan 89

We describe a patient with allergic granulomatous angitis who developed autoimmune hemolytic anemia (AIHA). A 44-year-old male had been suffering from bronchial asthma. On admission, laboratory tests revealed the presence of severe eosinophilia (21,500/microliters), elevation of total immunoglobulin E (IgE), high lactic dehydrogenase (LDH) and low haptoglobin levels, in addition to moderate reticulocytosis. During admission, the patient showed almost simultaneous occurrence of vasculitis in the extremities, severe hemolysis and exacerbation of asthma in relation to the progression of eosinophilia. Both IgM and IgG autoantibodies were considered to be responsible for hemolysis. Interestingly, serum levels of interleukin-4 (IL-4) and IL-5 were increased in association with eosinophilia and increased IgE production. These findings suggest that the AIHA in this patient is mediated or enhanced at least partly by high IL-4 and IL-5 production. Although AIHA in this syndrome is very rare, it should be considered as a clinical manifestation.
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PMID:Autoimmune hemolytic anemia in allergic granulomatous angitis (Churg-Strauss syndrome). 886 25

Peripheral and tissue eosinophilia are associated with a wide variety of inflammatory syndromes. These include both multisystem and limited diseases with vasculitis or non-vasculitic tissue damage and variable expression of end-stage-fibrosis. The idiopathic hypereosinophilic syndrome (IHS) represents a multisystem disorder defined by sustained eosinophilia of an undetectable cause with significant organ system dysfunction. Although not specified as such in the criteria for the diagnosis of IHS, there are idiopathic eosinophilic syndromes that are clinically distinct from IHS by virtue of the fact that the eosinophilic inflammation is limited to specific tissues (such as the skin) with an overall good prognosis. The pathogenic role of the eosinophilic granulocyte in these conditions is attested by evidence of eosinophil activation and degranulation at sites of tissue injury. The recruitment and localization of eosinophils to specific sites of tissue inflammation involves cytokines with haematopoietic growth factor activity, adhesion molecules expressed both by the vascular endothelium and eosinophils, and chemoattractants that stimulate eosinophil migration. Recently, overexpression of IL-5 in transgenic mice was shown to lead to both peripheral blood eosinophilia and tissue eosinophilia. With the advances in our understanding of cytokine-dependent regulatory mechanisms that control the peripheral eosinophil number as well as the recruitment and survivability of eosinophils at sites of inflammation, more targeted ways of manipulating the eosinophil reaction can be expected in the future.
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PMID:[Idiopathic eosinophilia]. 918 84

A 50-year-old woman with allergic granulomatous angiitis (AGA) presented with an elevated serum interleukin-5 (IL-5) level upon admission to a hospital. Administration of prednisolone showed marked improvement of asthmatic symptoms, reduced eosinophil counts of peripheral blood, and normalized serum IL-5 levels. This is the first report describing an elevated serum level of IL-5 in AGA. The present findings suggest that IL-5 is involved in the pathogenesis of AGA.
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PMID:Serum interleukin-5 levels in a case with allergic granulomatous angiitis. 937 32

Wegener's granulomatosis (WG) is a granulomatous vasculitis that affects the upper respiratory tract, lung, and kidney. Since T cells make up a significant proportion of cells infiltrating granulomatous lesions in WG, we investigated the proliferative response and cytokine profile of T cells from these patients. PBMCs were isolated from 12 patients with active WG, 7 patients with inactive disease, and 12 healthy normal donors. PBMCs from clinically active WG patients exhibited increased proliferation following stimulation with either PMA/ionomycin or anti-CD2 and anti-CD28, when compared with normal donors. In addition, these PBMCs exhibited increased secretion of IFN-gamma, but not of IL-4, IL-5, or IL-10. Furthermore, TNF-alpha production from PBMCs and CD4+ T cells isolated from patients with WG was elevated, when compared with healthy donors. In further studies, we investigated the ability of WG patients' monocytes to produce IL-12 and showed that both inactive and active patients produced increased amounts of IL-12. Finally, the in vitro IFN-gamma production by WG PBMC is inhibited in a dose-dependent manner by exogenous IL-10. These data suggest that T cells from WG patients overproduce IFN-gamma and TNF-alpha, probably due to dysregulated IL-12 secretion, and that IL-10 may therefore have therapeutic implications for this disease.
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PMID:Active Wegener's granulomatosis is associated with HLA-DR+ CD4+ T cells exhibiting an unbalanced Th1-type T cell cytokine pattern: reversal with IL-10. 953 24

Endothelial cells, by virtue of their capacity to express adhesion molecules and cytokines, are intricately involved in inflammatory processes. Endothelial cells have been shown to express interleukin-1 (IL-1), IL-5, IL-6, IL-8, IL-11, IL-15, several colony-stimulating factors (CSF), granulocyte-CSF (G-CSF), macrophage CSF (M-CSF) and granulocyte-macrophage CSF (GM-CSF), and the chemokines, monocyte chemotactic protein-1 (MCP-1), RANTES, and growth-related oncogene protein-alpha (GRO-alpha). IL-1 and tumor necrosis factor-alpha (TNF-alpha) produced by infiltrating inflammatory cells can induce endothelial cells to express several of these cytokines as well as adhesion molecules. Induction of these cytokines in endothelial cells has been demonstrated by such diverse processes as hypoxia and bacterial infection. Recent studies have demonstrated that adhesive interactions between endothelial cells and recruited inflammatory cells can also signal the secretion of inflammatory cytokines. This cross-talk between inflammatory cells and the endothelium may be critical to the development of chronic inflammatory states. Endothelial-derived cytokines may be involved in hematopoiesis, cellular chemotaxis and recruitment, bone resorption, coagulation, and the acute-phase protein synthesis. As many of these processes are critical to the maturation of an inflammatory and reparative state, it appears likely that endothelial-derived cytokines play a crucial role in several diseases, including atherosclerosis, graft rejection, asthma, vasculitis, and sepsis. Genetic and pharmacologic manipulation of endothelial-derived cytokines provides an additional approach to the management of chronic inflammatory diseases.
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PMID:Human endothelium as a source of multifunctional cytokines: molecular regulation and possible role in human disease. 1009 Mar 94

Wegener's granulomatosis (WG) and microscopic polyangiitis are systemic autoimmune diseases characterized by the presence of ANCA in the sera of patients. Little is known about the aetiologic factors and genetic predisposition as well as the pathogenesis of these disease entities. A slightly decreased representation of HLA-DRB1*13 and HLA-DQB1*0603 individuals was observed in our cohort of ANCA-associated systemic vasculitis (AASV) patients compared with controls. In addition, HLA-DRB1*04 individuals were over-represented in a subgroup of patients with WG in end-stage renal disease as a result of renal vasculitis. In order to identify other genes relevant for these diseases, we investigated highly polymorphic markers in the vicinity of several immunorelevant genes, i.e. tumour necrosis factor (TNF)alpha, IL-2, IL-5 receptor alpha (IL-5RA), in a group of 102 patients with AASV and compared the representation with controls. Furthermore, functional polymorphisms were directly analysed in the promotor region of TNFalpha as well as in the coding region of the FcgammaIIRA genes. Polymorphisms of the TNFalpha promotor (TNF-308) as well as in the FcgammaIIRA gene were excluded as risk factors for the disease in our cohort. No major phenotype distribution differences were observed between patients and controls for the IL-2 and IL-5RA microsatellites. Most importantly, several haplotypes on chromosome 6p appeared strongly associated with proteinase 3 (PR3)-ANCA+ AASV. Thus, as in other autoimmune diseases, different predisposing factors play differential aetiopathogenic roles in various groups of AASV patients.
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PMID:Immunogenetic risk factors for anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis. 1044 78

Experimental autoimmune uveoretinitis (EAU) is a T-cell-mediated autoimmune disease induced by immunization with uveitogenic retinal antigens, or by the adoptive transfer of uveitogenic T-cells of the Th-1-like phenotype. We have previously shown that IFN-gamma-deficient mice (GKO) on the C57BL/6 background are equally susceptible to interphotoreceptor retinoid binding protein (IRBP)-induced EAU as the wild type (WT). In the present study, we evaluated EAU induction in GKO mice by the newly described H-2(b)epitope contained in residues 1-20 of human IRBP, and compared it to the response to the whole IRBP molecule. Similarly to previous observations with IRBP-induced EAU, delayed type hypersensitivity (DTH) and lymphocyte proliferation responses were elevated in GKO mice, as was production of IL-5 and TNF-alpha. However, unlike the responses induced by whole IRBP, there was no detectable IL-10 production to the peptide. Histopathology on day 21 after immunization, revealed that both GKO and WT mice developed retinal lesions, including damage to the photoreceptor cell layer, vasculitis and inflammatory cellular infiltration, but disease scores were significantly higher in GKO, and retinal detachment was observed only in GKO mice. In contrast to the wild type, the cellular infiltrate in eyes of GKO mice contained a prominent component of eosinophils, although of lower proportion in peptide-induced than in IRBP-induced EAU. We conclude that the cytokine and inflammatory responses to human peptide 1-20 differ perceptibly from the responses to whole bovine IRBP, and may explain the elevated EAU scores of GKO mice compared to wild type.
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PMID:Residues 1-20 of IRBP and whole IRBP elicit different uveitogenic and immunological responses in interferon gamma deficient mice. 1093 Mar 16

Churg-Strauss syndrome (CSS) is a form of primary vasculitis characterized by allergy and angiitis. In the organ systems involved (lung, heart, peripheral nervous system, and so forth), eosinophilic infiltration can be found. Eosinophilia and normochromic normocytic anemia are leading laboratory findings together with elevated IgE. New seromarkers for the activation of endothelial cells, lymphocytes, and eosinophils (soluble thrombomodulin, soluble interleukin-2 receptor, eosinophil cationic protein) may be able to predict a relapse. Antineutrophil cytoplasmic antibodies are found in only approximately 50% of all patients with CSS, and their diagnostic value is questionable. Etiologically, hyperresponsiveness to an antigenic stimulus seems to underlie the syndrome. In asthmatics, cysteinyl leukotriene receptor type 1 antagonists are reported to trigger the disease. Cytokine profile findings on the cells involved in CSS remain contradictory. Some think CSS may be a Th2-mediated disease; its pathophysiology is not known fully. Interleukin-5 and tumor necrosis factor-alpha are elevated in serum and fluid of bronchoalveolar lavage, suggesting target cytokines for future treatment protocols. Treatment consists of glucocorticoid monotherapy. Data on outcome and effectiveness is lacking for other immunosuppressive regimens, such as cyclophosphamide or glucocorticoid plus cyclophosphamide. Treatment with interferon-alpha has been effective in patients refractory to glucocorticoid plus cyclophosphamide.
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PMID:Churg-Strauss syndrome: update on recent developments. 1179 Sep 90


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