Proinflammatory Cytokines and Autoimmunity in Churg-Strauss Syndrome
- 1 June 2005
- journal article
- review article
- Published by Wiley in Annals of the New York Academy of Sciences
- Vol. 1051 (1), 121-131
- https://doi.org/10.1196/annals.1361.053
Abstract
Churg-Strauss syndrome (CSS) belongs to the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides and is further characterized by severe eosinophilia and, often, granulomatous inflammation. The therapeutic efficacy of recombinant interferon-alpha (IFN-alpha) and tumor necrosis factor-alpha (TNF-alpha) blockade point toward a central role of cytokines in the pathogenesis of CSS. Recent data show that, in contrast to other primary systemic vasculitides, peripheral blood mononuclear cells (PBMCs) secrete not only large amounts of T helper type 1 (Th1) cytokines, particularly IFN-gamma, but also release T helper type 2 (Th2) cytokines such as interleukin-4 (IL-4) and interleukin-13 (IL-13). Interleukin-5 is the most potent stimulator of eosinophil production and functional activation of mature eosinophils, the key effector cells in CSS. Data are presented showing that PBMCs from patients with CSS cultured with T cell-specific stimuli secrete significantly increased amounts of IL-5 compared with healthy controls, suggesting that IL-5 contributes substantially to the development of eosinophilia in CSS. As recombinant IFN-alpha downregulates IL-5 production of CD4(+) T cells in vitro, the increased secretion of IL-5 in patients with CSS may provide the clue for the therapeutic efficacy of recombinant IFN-alpha in the disease. Variations in the balance between Th1 and Th2 cytokines at different disease stages could contribute to the distinct clinical courses seen in patients with CSS, which can range from prominent Th1-mediated generalized vasculitis and granulomatous inflammation on one end of the spectrum to Th2-mediated systemic hypereosinophilia on the other. Although the association of ANCAs with CSS point toward an autoimmune origin of the disease, there is no direct evidence as yet for a direct pathogenic role of ANCAs in CSS.Keywords
This publication has 41 references indexed in Scilit:
- Eosinophils function as antigen-presenting cellsJournal of Leukocyte Biology, 2004
- The FIP1L1-PDGFRα fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and managementBlood, 2004
- Activation of Arterial Wall Dendritic Cells and Breakdown of Self-tolerance in Giant Cell ArteritisThe Journal of Experimental Medicine, 2004
- Churg-Strauss-Syndrom unter Behandlung mit Leukotrien-Rezeptor-AntagonistenDeutsche Medizinische Wochenschrift (1946), 2003
- Prevalence of serious eosinophilia and incidence of Churg-Strauss syndrome in a cohort of asthma patientsAnnals of Allergy, Asthma & Immunology, 2002
- Epidemiology of systemic vasculitis: A ten-year study in the United KingdomArthritis & Rheumatism, 2000
- Abnormal Clones of T Cells Producing Interleukin-5 in Idiopathic EosinophiliaNew England Journal of Medicine, 1999
- Involvement of Soluble CD95 in Churg-Strauss SyndromeThe American Journal of Pathology, 1999
- Nomenclature of Systemic VasculitidesArthritis & Rheumatism, 1994
- Human eosinophils from hypereosinophilic patients spontaneously express the p55 but not the p75 interleukin 2 receptor subunitEuropean Journal of Immunology, 1991