Critical Involvement of Cytokines and Chemokines in the Pathogenesis of Rheumatoid Vasculitis

Vasculitis in rheumatoid arthritis (rheumatoid vasculitis) has a heterogeneous clinical presentation that includes skin disorders, neuropathy, eye symptoms and systemic infl ammation. The molecular mechanisms underlying rheumatoid vasculitis are not fully understood; however, the importance of a chronic imbalance of the cytokines and chemokines involved in orchestrating infl ammatory responses is well established in patients with rheumatoid arthritis, and similar dysregulation of these mediators has been suggested to occur in patients with rheumatoid vasculitis. In the present review, we discuss the involvement of cytokines and chemokines in the pathogenesis of rheumatoid vasculitis and evaluate their utility as laboratory parameters of active vasculitic disease. Also the involvement of adhesion molecules is discussed. Introduction Rheumatoid vasculitis (RV) is an uncommon but severe complication of rheumatoid arthritis (RA) that can cause skin disorders, neuropathy, eye symptoms and systemic infl ammation (Vollertsen and Conn, 1990; Genta et al. 2006). Although it is well known that chronically imbalanced expression of cytokines and chemokines is important for orchestrating the infl ammatory responses observed in RA patients (Kunkel et al. 1996a; Choy and Panayi, 2001; Firestein, 2003; McInnes and Schett, 2007), the pathogenesis of RV is still not fully understood. RV is defi ned histologically as vasculitis with an infl ammatory infi ltrate and destruction of the vessel wall (Vollertsen and Conn, 1990; Bacons and Kitas, 1994; Voskuyl et al. 2003) induced by circulating immune complexes containing rheumatoid factor (RF) and autoantibodies, which form deposits on vessel walls and trigger infl ammatory reactions that lead to endothelial cell (EC) activation and injury (Scott et al. 1981; Breedveld et al. 1988). Although the precise mechanisms underlying the pathogenesis of RV have not yet been resolved, it has been suggested that dysregulation of cytokine and chemokine networks, like that which occurs in RA, also occurs in RV. The purpose of this review is to provide an overview of the involvement of cytokines, chemokines and also adhesion molecules in the pathogenesis of RV and to evaluate their utility as laboratory parameters of active vasculitic disease. ECs Act as Vasculitic Effectors Although the causes of most vasculitic syndromes remain unclear, advances in molecular and cellular immunology have enabled many of the effector mechanisms that underlie infl ammatory vascular damage to be defi ned. ECs play a pivotal role in the pathogenesis of systemic vasculitis, and vascular endothelial dysfunction is a well studied feature of a variety of immune-mediated infl ammatory diseases, including vasculitis (Sneller and Fauci, 1997; Cid et al. 2004; Buckley et al. 2005; Kaneider et al. 2006; Bacon, 2005). ECs engage a number of proinfl ammatory activities, including expression and secretion of various cytokines, chemokines, cell adhesion molecules and other infl ammatory mediators (Mantovani and Dejana, 1989). Specifi c cell-cell interactions, especially between ECs and invading mononuclear cells, are key contributors to the progression of vasculitis and autoimmune diseases such as RA and systemic lupus erythematosus (SLE). Another important feature of infl ammatory and immune responses is expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 Clinical Medicine: Arthritis and Musculoskeletal Disorders 2008:1 1–8