Interleukin-32 (IL-32) is a cytokine involved in a broad repertoire of immunopathological events across both physiological and disease contexts, encompassing immune modulation, inflammatory amplification, and tumor initiation and progression. IL-32 propagates systemic inflammatory cascades by vigorously inducing pivotal mediators such as TNF-α and IL-17. Consequently, its dysregulated expression has been implicated in diverse disorders, and it has emerged as a tractable therapeutic target. Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent inflammatory synovitis that inexorably erodes articular cartilage and subchondral bone, resulting in debilitating pain, swelling, joint stiffness, and irreversible functional decline. IL-32 is markedly upregulated in the RA synovium, synovial fluid, and peripheral blood, and its abundance is positively correlated with clinical indices of disease activity. Mechanistically, IL-32 induces several cytokines in RA especially TNF-α and IL-17-two master cytokines of RA pathogenesis-thereby amplifying synovial inflammation, osteoclastogenesis, and subsequent joint destruction. Preclinical studies have demonstrated that genetic or pharmacologic inhibition of IL-32 attenuates experimental arthritis severity, underscoring its therapeutic potential. Herein, we provide a comprehensive, up-to-date review of the current understanding of IL-32 biology in RA and its translational implications.
Zhang et al. (Wed,) studied this question.