Inflammation Resolution and Nutritional Modulation of Equine Joint Health: Experimental Models, Biomarkers, and Functional Outcomes

Joint inflammation is a major cause of lameness and reduced athletic performance in horses. This thesis aimed to characterize early equine joint inflammation using complementary in vivo and in vitro models and evaluate the effects of oral nutraceutical supplementation on inflammatory, cartilage metabolic, and pro-resolving responses. Study 1: A low-dose recombinant equine interleukin-1β (reIL-1β) synovitis model was developed to identify a dose capable of inducing measurable biochemical and functional responses without overt lameness. In three horses, intra-articular administration of 75ng reIL-1β produced mild, transient inflammation characterized by increased synovial fluid prostaglandin E₂ (PGE₂). Objective gait analysis detected changes in poll movement asymmetry associated with PGE₂ concentrations, although these remained within reported inter-session variability. Study 2: The 75ng model was further evaluated in 11 horses using inflammatory, cartilage turnover, and pro-resolving biomarkers alongside objective gait analysis. Increased synovial fluid PGE₂ and nitric oxide (NO) occurred following reIL-1β administration, while movement asymmetries remained within reported biological variability, supporting the non-clinical, transient nature of the model. Study 3: Using this inflammatory model, a low ratio omega-3:6 polyunsaturated fatty acid nutraceutical (STRUCTURE-Joint) increased synovial fluid NO, PGE₂, and resolvin D1 (RvD1), while reducing joint circumference and altering systemic blood parameters. These findings suggest modulation of inflammatory and pro-resolving pathways rather than suppression of inflammation. Study 4: A nutraceutical containing sodium hyaluronate, Boswellia serrata extract, and curcumin reduced joint circumference and synovial fluid NO and CS846 concentrations following inflammatory challenge, indicating modulation of inflammatory signaling and cartilage metabolism. Study 5: An in vitro lipopolysaccharide-stimulated porcine cartilage explant model evaluated whether STRUCTURE-Joint acted directly on cartilage. Supplementation did not reduce NO or glycosaminoglycan production; however, high-dose supplementation increased RvD1 under inflammatory conditions, supporting a potential role in inflammation resolution rather than direct chondroprotection. Collectively, this thesis establishes a reproducible model of transient, subclinical synovitis and demonstrates formulation-specific nutraceutical effects on inflammatory signaling, cartilage metabolism, and pro-resolving pathways. These findings provide an experimental framework for evaluating nutritional strategies aimed at supporting equine joint health and performance.