Cell trafficking, mediator release, and articular metabolism in acute inflammation of innervated or denervated isolated equine joints.

Abstract

OBJECTIVES To describe the acute cellular response, inflammatory mediator release, and effect on chondrocyte metabolism of interleukin 1 beta (IL-1 beta) in isolated innervated or denervated equine metacarpophalangeal joints. ANIMALS One metacarpophalangeal joint of 24 adult horses. PROCEDURES The metacarpophalangeal joint was isolated for 6 hours in a pump-perfused, auto-oxygenated, innervated or denervated metacarpophalangeal joint preparation. Isolated joints were assigned to 4 groups: control, control-denervated, inflamed, and inflamed-denervated, and inflammation was induced by intra-articular injection of IL-1 beta. Synovial fluid was collected for cytologic examination and determination of IL (IL)-1 beta, (IL-6), prostaglandin E2 (PGE2), and substance P (SP) values. Synovial membrane was immunostained with SP and nerve-specific enolase (NSE) antibodies. Cartilage was collected for determination of proteoglycan (PG) synthesis and degradation. RESULTS IL-1 beta induced significant neutrophilic leukocytosis in synovial and synovial membrane. IL-1 beta concentration and returned to baseline by 5.5 hours, but IL-6 concentration significantly increased throughout the study. Total SP content was significantly higher in inflamed joints. There was a significant increase in 24- and 48-hour PG degradation in inflamed innervated joints. CONCLUSION Cellular response to IL-1 beta was rapid and sustained; joint clearance of IL-1 beta was rapid, and endogenous production of IL-1 beta did not follow. The IL-6 and PGE2 concentrations significantly increased, and SP content was increased in association with inflammation but not denervation. A degradative response of cartilage of IL-1 beta was observed, and was enhanced by innervation. This model was useful for investigation of the articular response to acute inflammation and the influence of denervation in modulating this response.

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