{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:23:03Z","timestamp":1790353383672,"version":"4.1.0"},"reference-count":141,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Interleukin-1\u03b2 (IL-1\u03b2) 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-1\u03b2 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-1\u03b2 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-1\u03b2 and IL-18 on resident cells during knee OA progression. Despite substantial evidence suggesting that cytokines are involved in OA progression, IL-1\u03b2-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-1\u03b2\/IL-18 signaling pathway, emphasizing the significance of biomarker-driven and combination therapies for improving OA management.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1870390","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:41:14Z","timestamp":1784785274000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring the intricate relationship between IL-1\u03b2 and IL-18 in the context of osteoarthritis"],"prefix":"10.3389","volume":"17","author":[{"given":"Anjali","family":"Kumari","sequence":"first","affiliation":[{"name":"Immunopathology Lab, School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil N\u0101du, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahaboobkhan","family":"Rasool","sequence":"additional","affiliation":[{"name":"Immunopathology Lab, School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil N\u0101du, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1080\/03008207.2025.2502591","article-title":"Mechanical insights into fat pads: a comparative study of infrapatellar and suprapatellar fat pads in osteoarthritis","volume":"66","author":"Pettenuzzo","year":"2025","journal-title":"Connect Tissue Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2020.100587","article-title":"Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies","author":"Cui","year":"2020","journal-title":"EClinicalMedicine"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.872155","article-title":"What is IL-1 for? 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