Synovial fluid cytokines and eicosanoids as markers of joint disease in horses

Objective-To evaluate the value of various synovial fluid cytokines and eic osanoids to diagnose joint disease or categories of joint disease. Study Design-Prospective acquisition of clinicopathologic data. Animals or Sample Population-Client-owned or donated horses: 50 joints with no evidence of disease; 28 joints with acute disease; 32 joints with chron ic disease; 9 joints with cartilage damage and no other signs of joint dise ase. Methods-Concentrations of tumor necrosis factor-alpha (TNF-alpha), interleu kin-1 beta (IL-1 beta), interleukin-6 (IL-6), prostaglandin E-2 (PGE(2)), t hromboxane B-2 (TXB2), prostaglandin F1-alpha (PGF(1)-alpha), and leukotrie ne B-4 (LTB4), were measured in equine synovial fluid by immunoassay and ca tegorized according to duration and degree of joint disease. Any test value for a given category that was different from normal was further analyzed f or sensitivity (S), specificity (Sp), and operating point (most valid test cutoff value). Likelihood ratios and predictive values were calculated at t he operating point. Mediator concentrations were correlated to synovial flu id white blood cell count. Tests were reported as poor, fair, good, or exce llent based on predictive values of <25, .25-.5, .5-75, or >.75, respective ly. Results-TNF synovial fluid concentration as a predictor of joint disease wa s good, and the value of TNF (maximum S and Sp) indicating joint disease wa s >36 pg/mL. IL-1 beta as a predictor of joint disease was good, and the va lue of IL-1 beta indicating joint disease was >4.5 pg/mL. IL-6 concentratio n was an excellent predictor of joint disease. Any IL-6 in synovial fluid i ndicated joint disease and correlated highly with synovial fluid white bloo d cell count (P<.0001). PGE(2) was a good-excellent predictor of disease (p ositive predictive value [PPV] = 0.75), and the concentration indicating jo int disease was >22.5 pg/mL. The diagnostic PGF(1)-alpha concentration indi cating severe chronic joint disease was identified to be >16.5 pg/mL with v ery high sensitivity (S=1) and specificity (Sp=.89). PGF(1)-alpha concentra tions >9.5 pg/mL had a good PPV (.69) and NPV (.6) for any joint disease. T BX2 concentrations below 31.5 pg/mL (S=.57; Sp=.61) were a very good predic tor of joint disease (PPV=.72). LTB4 concentration appeared to be greater i n severe acute joint disease than normal joints; this was not significant ( P=.15) and correlated highly with synovial fluid white blood cell count (P= .0001). Conclusions-The ability of a single value from a joint in an adult horse pr edicting the presence of joint disease was often good (.5-.75), and was exc ellent (greater than or equal to .75) for IL-6 and PGE(2). TNF-alpha and IL -1 beta were no more effective than white blood cell count in screening, fo r joint disease. IL-6 was the most sensitive and specific for joint disease and could be an excellent screening test for the presence of joint disease when lameness is difficult to identify or is intermittent. PGE(2) would be a functional screening test for the presence of any joint disease and offe rs a differentiating feature because values were not influenced by white bl ood cell count. PGF(1)-alpha values >16.5 pg/mL identified chronic severe j oint disease and may be clinically useful when there are minimal radiograph ic changes but substantial articular cartilage degradation. (C) Copyright 2 001 by The American College of Veterinary Surgeons.