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

Tumor necrosis factor‑α (TNF‑α) is a pleiotropic pro‑inflammatory cytokine that contributes to the pathophysiology 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 function 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.