Objective: To synthesize evidence on the role of cytokines in the pathogenesis of knee osteoarthritis and to update biologic and cartilage-regenerative therapies with potential to influence disease progression.
Methods: A focused narrative review was conducted using PubMed/MEDLINE, the Cochrane Library, and ClinicalTrials.gov, with the search updated to October 12, 2025. Priority was given to recent practice guidelines, meta-analyses, pivotal clinical trials, and mechanistic reviews addressing IL-1β, TNF-α, and IL-6.
Results: Knee osteoarthritis is now regarded as a whole-joint disorder characterized by low-grade inflammation, synovitis, senescence-associated inflammatory signaling, and cytokine-driven catabolic pathways. IL-1β, TNF-α, and IL-6 promote cartilage matrix degradation by activating intracellular inflammatory and catabolic signaling pathways, including NF-κB, MAPK (mitogen-activated protein kinase), and JAK/STAT (Janus kinase/signal transducer and activator of transcription), whereas single-cytokine blockade has shown limited clinical benefit. Sprifermin increases cartilage thickness, although symptomatic improvement remains inconsistent; lorecivivint has shown encouraging phase 2b signals; and anti-nerve growth factor therapy reduces pain but remains constrained by joint safety concerns. PRP may improve pain and function in selected patients, but its effects depend on product characteristics. MSC-derived exosomes represent a promising cell-free therapeutic strategy, although clinical evidence remains early.
Conclusions: Cytokines play a central role in the pathogenesis of knee osteoarthritis, but blocking individual nodes is unlikely to provide durable benefit.