Effects of oral administration of phenylbutazone to horses on in vitro articular cartilage metabolism

Objective-To evaluate the effects of orally administered phenylbutazone on proteoglycan synthesis and chondrocyte inhibition by IL-1 beta in articular cartilage explants of horses. Animals-11 healthy 1- to 2-year-old horses. Procedure-Horses were randomly assigned to the control (n = 5) or treated g roup (4.4 mg of phenylbutazone/kg of body weight, PO, q 12 h; n = 6). Artic ular cartilage specimens were collected before treatment was initiated (day 0), after 14 days of treatment, and 2 weeks after cessation of treatment ( day 30). Proteoglycan synthesis and stromelysin concentration in cartilage extracts were assessed after 72 hours of culture in medium alone or with re combinant human interleukin-1 beta (IL-1 beta; 0.1 ng/ml). Results-On day 0, proteoglycan synthesis was significantly less in cartilag e explants cultured in IL-1 beta, compared with medium alone. Mean proteogl ycan synthesis in explants collected on days 14 and 30 was significantly le ss in treated horses, compared with controls. However, incubation of explan ts from treated horses with IL-1 beta did not result in a further decrease in proteoglycan synthesis. Significant differences in stromelysin concentra tion were not detected between or within groups. Conclusions and Clinical Relevance-Oral administration of phenylbutazone fo r 14 days significantly decreased proteoglycan synthesis in articular cultu re explants from healthy horses to a degree similar to that induced by in v itro exposure to IL-1 beta. Phenylbutazone should be used judiciously in at hletic horses with osteoarthritis, because chronic administration may suppr ess proteoglycan synthesis and potentiate cartilage damage.