Tumor necrosis factor-α in systemic lupus erythematosus: Structure, function and therapeutic implications (Review)

Abstract

Tumor necrosis factor-α (TNF-α) is a pleiotropic pro-inflammatory cytokine that contributes to the patho- physiology of several autoimmune diseases, such as multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, psoriatic arthritis and systemic lupus erythematosus (SLE). The specific role of TNF-α in autoimmunity is not yet fully understood however, partially, in a complex disease such as SLE. Through the engagement of the TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2), both the two variants, soluble and transmembrane TNF-α, can exert multiple biological effects according to different settings. They can either func- tion as immune regulators, impacting B-, T- and dendritic cell activity, modulating the autoimmune response, or as pro-inflammatory mediators, regulating the induction and maintenance of inflammatory processes in SLE. The present study reviews the dual role of TNF-α, focusing on the different effects that TNF-α may have on the pathogenesis of SLE. In addition, the efficacy and safety of anti-TNF-α therapies in preclinical and clinical trials SLE are discussed.