Contribution of Interleukin-6 to the Pathogenesis of Systemic Sclerosis

Abstract

Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology, manifesting in patients as tissue fibrosis, endothelial dysfunction, and inflammation. The disease is characterized by autoantibodies, a hallmark of autoimmunity. Various cytokines and growth factors are elevated in the systemic circulation and fibrotic lesions of patients with SSc. In particular, several studies over the past 2 decades have shown that interleukin-6 (IL-6) appears to be involved in the pathogenesis of SSc. Based on the association between aberrant IL-6 production and tissue fibrosis in patients with SSc, the anti-IL-6 receptor antibody, tocilizumab, is being investigated in clinical trials. This article reviews the biological features of IL-6 and the IL-6 receptor; the role of IL-6 in the pathogenesis of SSc; and the potential for IL-6 inhibition to be used in the treatment of patients with SSc.