Interleukin-6 (IL-6) is a multifunctional cytokine involved in immune regulation, inflammation, hematopoiesis, and tissue repair. It binds to membrane-bound IL-6 receptors (IL-6R) or soluble IL-6R, activating downstream signaling via glycoprotein 130 (gp130), which triggers pathways like JAK/STAT, MAPK, and PI3K. Dysregulated IL-6 signaling is linked to chronic inflammation, autoimmune diseases (e.g., rheumatoid arthritis), and cancers.
IL-6-targeting antibodies were developed to block this pathway. Two main strategies exist: antibodies against IL-6 itself (e.g., siltuximab) or IL-6R (e.g., tocilizumab, sarilumab). Tocilizumab, a humanized anti-IL-6R monoclonal antibody, was first approved in 2010 for rheumatoid arthritis and later for cytokine release syndrome (CRS) in CAR-T therapy and severe COVID-19. Siltuximab, targeting IL-6 directly, is used for multicentric Castleman’s disease. These antibodies reduce inflammation, alleviate symptoms, and improve clinical outcomes.
Research continues to explore their roles in other IL-6-driven conditions, such as certain cancers and inflammatory syndromes. Challenges include managing side effects (e.g., infections, elevated liver enzymes) and optimizing therapeutic efficacy through combination therapies. IL-6 antibodies represent a cornerstone in precision medicine for immune-mediated diseases.