Role of IL-32 in RA pathology and potential as a drug target

TL;DR

This paper explores how IL-32 contributes to rheumatoid arthritis and its potential as a drug target for treating the disease.

Contribution

The paper provides a comprehensive and up-to-date review of IL-32's role in rheumatoid arthritis and its therapeutic potential.

Findings

IL-32 is upregulated in rheumatoid arthritis and correlates with disease activity.

Inhibiting IL-32 reduces arthritis severity in preclinical models.

IL-32 amplifies inflammation and joint destruction by inducing TNF-α and IL-17.

Abstract

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.

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