Abstract: To evaluate the value of various synovial fluid cytokines and eicosanoids to diagnose joint disease or categories of joint disease. Methods: Prospective acquisition of clinicopathologic data. Methods: Client-owned or donated horses: 50 joints with no evidence of disease; 28 joints with acute disease; 32 joints with chronic disease; 9 joints with cartilage damage and no other signs of joint disease. Methods: Concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), prostaglandin E(2) (PGE(2)), thromboxane B(2) (TXB(2)), prostaglandin F1-alpha (PGF(1)-alpha), and leukotriene B(4) (LTB(4)), were measured in equine synovial fluid by immunoassay and categorized according to duration and degree of joint disease. Any test value for a given category that was different from normal was further analyzed for sensitivity (S), specificity (Sp), and operating point (most valid test cutoff value). Likelihood ratios and predictive values were calculated at the operating point. Mediator concentrations were correlated to synovial fluid white blood cell count. Tests were reported as poor, fair, good, or excellent based on predictive values of .75, respectively. Results: TNF synovial fluid concentration as a predictor of joint disease was good, and the value of TNF (maximum S and Sp) indicating joint disease was >36 pg/mL. IL-1beta as a predictor of joint disease was good, and the value of IL-1beta indicating joint disease was >4.5 pg/mL. IL-6 concentration was an excellent predictor of joint disease. Any IL-6 in synovial fluid indicated joint disease and correlated highly with synovial fluid white blood cell count (P 22.5 pg/mL. The diagnostic PGF(1)-alpha concentration indicating severe chronic joint disease was identified to be >16.5 pg/mL with very high sensitivity (S = 1) and specificity (Sp =.89). PGF(1)-alpha concentrations > 9.5 pg/mL had a good PPV (.69) and NPV (.6) for any joint disease. TBX(2) concentrations below 31.5 pg/mL (S =.57; Sp =.61) were a very good predictor of joint disease (PPV =.72). LTB(4) concentration appeared to be greater in 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 predicting the presence of joint disease was often good (.5-.75), and was excellent (> or =.75) for IL-6 and PGE(2). TNF-alpha and IL-1beta were no more effective than white blood cell count in screening for 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 offers a differentiating feature because values were not influenced by white blood cell count. PGF(1)-alpha values > 16.5 pg/mL identified chronic severe joint disease and may be clinically useful when there are minimal radiographic changes but substantial articular cartilage degradation.
Copyright 2001 by The American College of Veterinary Surgeons
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The research investigates the use of synovial fluid cytokines and eicosanoids in diagnosing joint diseases in horses. The study finds that certain elements in the fluid can predict the presence of joint disease, especially the cytokine interleukin-6 (IL-6), prostaglandin E(2) (PGE(2)), and prostaglandin F1-alpha (PGF(1)-alpha).
Research Objectives and Methods
The study aims to evaluate the usefulness of various synovial fluid cytokines and eicosanoids for diagnosing joint diseases or specific categories of joint disease in horses.
The study involves horses that are either client-owned or donated, with different health states: healthy, with acute joint disease, chronic joint disease, or cartilage damage with no other signs of joint disease.
The research looked at the concentrations of certain cytokines and eicosanoids (TNF-alpha, IL-1beta, IL-6, PGE(2), TXB(2), PGF(1)-alpha, and LTB(4)) in the horses’ synovial fluid, using immunoassay.
The study also calculated the sensitivity, specificity, operating point (i.e., the most valid test cutoff value), likelihood ratios, and predictive values of the tests. It further correlated the mediator concentrations to the synovial fluid’s white blood cell count.
Results and Findings
The concentration of TNF-alpha was good at predicting the presence of joint diseases, especially if the value was above 36 pg/mL.
The value of IL-1beta indicating joint diseases was considered good, specifically if it was greater than 4.5 pg/mL.
The concentration of IL-6 was considered an excellent predictor of a joint disease. Any candidate with IL-6 in their synovial fluid was likely to have joint disease, and this highly correlated with the synovial fluid white blood cell count.
PGE(2) was good to excellent in predicting the presence of the joint diseases if the concentration was greater than 22.5 pg/mL.
The concentration of PGF(1)-alpha indicating severe chronic joint disease was identified to be greater than 16.5 pg/mL.
The concentration of TBX(2) under 31.5 pg/mL was seen to be a good predictor for joint disease.
Greater concentrations of LTB(4) appeared more often in severe acute joint disease patients.
Conclusions
The study concludes that a single value from a joint can often predict the presence of joint disease effectively.
IL-6 and PGE(2) had an excellent (> or =.75) predictive ability.
The research found TNF-alpha and IL-1beta no more effective than white blood cell count in screening for joint diseases.
It recommends the use of IL-6 as a screening test for the presence of joint disease where lameness is difficult to identify or is intermittent, while PGE(2) would serve as a reliable screening test for any joint disease, indicating a differentiating feature as it isn’t influenced by the white blood cell count.
PGF(1)-alpha values greater than 16.5 pg/mL can be especially useful in identifying severe chronic joint diseases, particularly when radiographic changes are minimal but substantial articular cartilage degradation is apparent.
Cite This Article
APA
Bertone AL, Palmer JL, Jones J.
(2001).
Synovial fluid cytokines and eicosanoids as markers of joint disease in horses.
Vet Surg, 30(6), 528-538.
https://doi.org/10.1053/jvet.2001.28430
Orthopedic Research Laboratory, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210-1089, USA.
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Oprenyeszk F, Sanchez C, Dubuc JE, Maquet V, Henrist C, Compère P, Henrotin Y. Chitosan enriched three-dimensional matrix reduces inflammatory and catabolic mediators production by human chondrocytes. PLoS One 2015;10(5):e0128362.
Labens R, Lascelles BD, Charlton AN, Ferrero NR, Van Wettere AJ, Xia XR, Blikslager AT. Ex vivo effect of gold nanoparticles on porcine synovial membrane. Tissue Barriers 2013 Apr 1;1(2):e24314.
Blewis ME, Lao BJ, Schumacher BL, Bugbee WD, Sah RL, Firestein GS. Interactive cytokine regulation of synoviocyte lubricant secretion. Tissue Eng Part A 2010 Apr;16(4):1329-37.
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