Lymphotoxin alpha revisited: general features and implications in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting synovial joints. Therapies blocking tumor necrosis factor-alpha (TNFalpha) are now routinely used in the management of RA. However, a significant number of patients with RA do not respond or develop resistance to anti-TNF therapies, and the participation of other cytokines in RA pathogenesis has been reported as well. Lymphotoxin alpha (LTalpha) is the closest homolog to TNFalpha and has been implicated in inflammation and autoimmunity since its original description in 1968. In spite of that, little is known about the role of LTalpha in RA or the potential of blocking this cytokine as an alternative therapeutic approach. In this review, we aim to summarize the general features of LTalpha and what is currently known about its participation in RA.