Cytokine-mediated pathophysiology of equine and human joint disease: mechanisms, biomarkers, and therapeutic targets.

Cytokine-mediated inflammation plays a central role in the pathogenesis of joint disease across species, contributing to synovial activation, cartilage degradation, and structural remodeling. In both equine and human medicine, key pro-inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-6, regulate intracellular signaling pathways such as NF-κB and JAK/STAT, driving matrix degradation and immune cell recruitment. This review synthesizes current knowledge on cytokine signaling in osteoarthritis, synovitis, and septic arthritis, highlighting conserved mechanisms and species-specific differences. Comparative evaluation reveals that while cytokine profiles are largely conserved, differences in magnitude and temporal dynamics influence disease progression and therapeutic response. Emerging diagnostic applications, including synovial fluid cytokine profiling, offer potential for early detection and prognostication. Therapeutic strategies targeting cytokines, including biologics, orthobiologics, gene therapy, and mesenchymal stromal cells, demonstrate translational relevance across species. Despite advances, limitations in assay standardization and longitudinal data remain significant barriers, particularly in equine research. Strengthening cross-species methodological alignment and integrating multi-omics approaches will be critical for advancing cytokine-targeted therapies and improving outcomes in joint disease.