Evaluation of the Inflammatory Response in Experimentally Induced Synovitis in the Horse: a Comparison of Recombinant Equine Interleukin 1 Beta and Lipopolysaccharide

Objective: To compare two transient models of synovitis-osteoarthritis (OA) in horses by characterizing biological changes in synovial fluid and joint tissue.

Method: Twelve skeletally mature mares were utilized in a block design. Synovitis was induced by an intra-articular injection of 100 ng recombinant equine interleukin 1 beta (reIL-1β) or 0.5 ng lipopolysaccharide (LPS) into a middle carpal joint in 1 ml volumes. One ml of saline was injected into the contra-lateral control joint. Lameness evaluations were conducted through post-injection hour (PIH) 8 (at which time arthroscopic removal of synovium and articular biopsies was done), and at PIH 240. Arthrocentesis collection of synovial fluid occurred between PIH 0 and 48. An arthroscopic examination at PIH 8 included synovium and articular cartilage biopsies for gene expression analysis.

Results: Synovial fluid analysis indicated that single injections of reIL-1β or LPS increased synovial white blood cell (WBC), neutrophil count, total protein, prostaglandin E(2) (PGE(2)) concentrations and general matrix metalloproteinase (MMP) activity relative to control joints through PIH 8. Injections of either reIL-1β or LPS increased mRNA expression for MMP-1 and a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-4 in synovium and for MMP-1, ADAMTS-4, ADAMTS-5 in articular cartilage collected at PIH 8 compared to saline injections.

Conclusion: Injections of reIL-1β into equine carpal joints resulted in a transient inflammatory response that was similar in severity to the LPS injection, causing increased expression of certain deleterious mediators in joint tissues at 8 h. Given that IL-1β is a known critical mediator of traumatic arthritis and OA, this humane and temporary model may be useful in evaluating therapeutics that act against early stages of joint disease.