Cytokines and Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by the production of numerous autoantibodies that typically involves multiple organ systems. As opposed to lupus in animal models, SLE in humans is heterogeneous and affects different individuals with a wide range of disease courses and manifestations. The pathogenesis is still unclear, a myriad of innate and adaptative immune system aberrations in SLE have been identified as major contributors of the disease. Cytokines are a diverse group of soluble proteins and peptides, produced and released by immune system cells , that act as humoral regulators and modulate the functional activities of individual cells and tissues, playing a pivotal role in the differentiation, maturation, and activation of various immune and no immune cells. Cytokine dysregulation is likely to play a role in the loss of immune tolerance that leads to SLE, and in the damage resulting from the disease. Many of the genes that are associated with risk for lupus are cytokines, regulators of cytokines, or downstream members of cytokine pathways. Multiple cytokines have been implicated in the disease activity or organ involvement in SLE. Among these, IL-6, Interferon (IFN), B-lymphocyte stimulator (BlyS), IL-10, IL-17 is thought to play an important role in the creation of the characteristic milieu in SLE, which promotes B-cell survival and autoantibody production. On the other hand, also cytokines like IL-10, IL1, TNF-┙ , IFN, are important in development of the autoimmune injury in renal and central nervous system, the most frequently observed causes of death in patients with SLE. Moreover, recent studies strongly suggest that the cytokines, at least in part, would be implicated in the pathogenesis of accelerated atherosclerosis associated with SLE. The knowledge of cytokines not only provides new insight into pathogenesis of SLE, but also it has allowed the development of clinical applications such as monitoring of disease and as potential therapeutic targets with the use of several biologic agents, targeting different cytokines or their receptors. Consequently, many trials of anticytokine therapies for SLE are underway. The focus of the present chapter is to summarize the cytokines which have significant implications in the pathogenesis of SLE, the potential clinical and therapeutic use will be reviewed.