Exploring the intricate relationship between IL-1β and IL-18 in the context of osteoarthritis

Interleukin-1β (IL-1β) and interleukin-18 (IL-18) are key members of the IL-1 cytokine family that contribute to the initiation and progression of osteoarthritis (OA). Although both cytokines share structural similarities and use MyD88-dependent signaling pathways, accumulating evidence indicates that they function complementarily rather than redundantly. IL-1β acts as an early catalyst for catabolic processes, leading to cartilage breakdown and cellular senescence, whereas IL-18 serves as an inflammasome-dependent enhancer that activates the immune response. This review summarizes the roles of IL-1β and IL-18 at multiple biological levels in OA progression and discusses their secretion and activation mechanisms. Additionally, we explore current and emerging pathological strategies that target the effects of IL-1β and IL-18 on resident cells during knee OA progression. Despite substantial evidence suggesting that cytokines are involved in OA progression, IL-1β-targeted therapies have shown limited clinical success, highlighting the need to explore additional targets. By integrating multiple pathological mechanisms, this review proposes a conceptual framework in which OA progression comprises three interconnected phases: cytokine-driven initiation, amplification, and chronicity, all linked to senescence. In conclusion, this review evaluates current pharmacological strategies. It underscores future research directions that focus on key elements of the IL-1β/IL-18 signaling pathway, emphasizing the significance of biomarker-driven and combination therapies for improving OA management.