Clinical Relevance of Cytokines, Chemokines and Adhesion Molecules in Systemic Vasculitis

Abstract

Although the causes of most vasculitis syndromes remain unclear, advances in molecular and cellular immunology have enabled the definition of many effector mechanisms that mediate inflammatory vascular damage. Vascular endothelial dysfunction is observed in a variety of immune-mediated inflammatory diseases. Therefore, endothelial cells (ECs) play a pivotal role in the pathogenesis of systemic vasculitis (Buckley et al. 2005; Kaneider et al. 2006), in large part by amplifying and perpetuating the inflammatory process through the expression and secretion of various cytokines, chemokines, cell adhesion molecules, and other inflammatory molecules. In addition, specific cell-cell interactions, especially between ECs and invading mononuclear cells, including macrophages and lymphocytes, also contribute to the progression of systemic vasculitis and other autoimmune diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, recent studies of the pathogenesis of atherosclerosis have shown that a key feature of atherosclerotic disease is the alternating interaction and amplification of thrombosis and inflammation, which is considered an unusual form of chronic inflammation of the artery wall that is triggered by chemical (e.g., smoking and hyperlipidemia), biological (e.g., Chlamydia pneumoniae) and/or mechanical (e.g., shear stress in hypertension) insults to ECs (Libby 2002). Among the various mediators secreted by activated inflammatory cells are cytokines and chemokines, which appear to be involved in both systemic vasculitis and atherosclerosis. The purpose of this review is to provide an overview of the expression and function of the cytokines and chemokines during the pathogenesis of vasculitic diseases, including systemic vasculitis and related conditions.