EXPERIMENTALLY-INDUCED SYNOVITIS AS A MODEL FOR ACUTE SYNOVITIS IN THE HORSE

The use of extremely small dosages of intra-articular E. coli lipopolysaccharide (LPS) endotoxin can create a model of synovitis that mimics acute synovitis in horses. Dosages of 5000 ng, 25 ng, 0.5 ng, 0.25 ng, 0.17 ng and 0.125 ng per joint were injected into various joints of a total of 6 horses. The dose response of LPS on clinical signs and synovial fluid parameters was evaluated at baseline and 12, 24, 36 and 48 h after LPS injection. Peripheral venous blood analysis was performed at baseline and at 0, 4, and 12 h after LPS injection. Dosages greater than 0.5 ng/joint resulted in clinical signs of endotoxaemia including fever, depression, inappetence and non-weightbearing lameness. Although the total peripheral venous leucocyte count was not decreased at any dosage, the 5000 ng/joint dosage of LPS altered venous leucocyte differential resulting in an increase in the number of segmented and band neutrophils with a concomitant decrease in lymphocytes. Synovial fluid total nucleated cell count (TNC) and total protein (TP) was linearly responsive to increases in intra-articular LPS dosages up to the 0.5 ng/joint dose. At dosages of LPS > 0.5 ng, synovial fluid mean +/- s.e.m. TNC and TP were 122.0 +/- 27 x 10(9) cells/l and 59.3 +/- 1.7 g/l respectively, at 12 h after injection. This may represent the maximal response of the joint to increased concentrations of LPS endotoxin over 0.5 ng/joint. The 0.125 ng dosage of LPS endotoxin resulted in a synovial fluid mean +/- s.e.m. TNC and TP of 31.5 +/- 4.3 x 10(9) cells/l and 40.2 +/- 2.3 g/l respectively, at 12 h after injection. At the 0.125 ng/joint dosage, horses exhibited mild to moderate effusion and warmth of the injected joint, mild resistance to palpation and a grade 2 lameness. Horses at this dosage continued to bear weight on the injected limb and eat throughout the 48 h study period. By the end of the 48 h study period joint effusion was decreased and lameness was subsiding. In a subsequent study, the response to repeated LPS at the 0.125 ng dosage was evaluated to determine the ability of the joint to respond and maintain the synovitis. Clinical and synovial fluid parameters were evaluated at baseline and 6, 12, 18, 24, 36, 48, 60, 96, 108, 144, and 156 h after intra-articular LPS at the 0.125 ng dosage. LPS injections were repeated immediately after the 48, 96 and 144 h arthrocentesis periods in an effort to maintain the synovitis for a period of one week. Synovial fluid parameters and clinical signs of lameness and joint effusion began to wane between 36 and 48 h after each repeated injection. However, the synovial membrane was capable of responding and maintaining the clinical and synovial fluid signs of synovitis over the study period with repeated LPS injections at the same 0.125 ng/joint dosage.