Selected cytokine pathways in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction. Cytokines play a key role in its pathogenesis. They contribute to the induction and maintenance of inflammation and thus provide therapeutic targets. Many cytokines are involved in RA, and this review focuses on a few critical ones: tumor necrosis factor (TNF), interleukin (IL)-6, IL-1, IL-17, and GM-CSF. TNF and IL-6 are both well-established targets in RA treatment, and new biologic agents are reaching the market. IL-1 represents a more complex cytokine as results in humans do not reach those in animal models. IL-17 and GM-CSF are cytokines representing new targets either as early treatment or in non-responders to other biologics. The interaction between cytokines and their signaling pathways are the basis for the development of new strategies with small molecules or bispecific antibodies. Clearly, the targeting of cytokines has been a major progress in RA treatment, but many issues remain open. Although remission can be better achieved, reactivation of the disease too often occurs upon treatment discontinuation. Better understanding and targeting of chronicity remains a goal to achieve in the future.