Expression of inflammatory and structural matrix genes in synovial fluid following intra-articular administration of isoflupredone acetate to exercised horses.

ABSTRACT

BACKGROUND: Intra-articular use of corticosteroids is commonplace in performance horses. Isoflupredone acetate (IPA) is one of four Food and Drug Administration approved corticosteroids for intra-articular use in horses. The lack of published reports describing the efficacy and duration of effects of this drug warrant further study. OBJECTIVES: To assess the effects of intra-articular administration of IPA on the expression of selected anti- and pro-inflammatory and structural matrix genes following intra-articular administration to exercised Thoroughbred horses and to correlate these effects with drug concentrations. STUDY DESIGN: Block design in vivo experiment. METHODS: Twelve exercised horses received either a single intra-articular administration of 8 mg of IPA or 0.9% saline solution. Synovial fluid samples were collected prior to and up to 42 days post drug administration from the treated joints. Microarray and qRT-PCR analysis were used to assess changes in expression levels of various inflammatory and structural genes post drug administration. RESULTS: On microarray analysis, 855, 23,358 and 26,411 genes had a measurable fold change (increase or decrease in expression levels) when comparing baseline samples to 24 h, baseline samples to day 7 and 24 h samples to day 7, respectively. Of the genes selected for further study by qRT-PCR analysis, expression of ANXA-1 (lipocortin) was significantly increased and IL23A and MMP1 and MMP9 significantly decreased following IPA administration. Expression levels of collagen genes were not significantly different from baseline. MAIN LIMITATIONS: Limitations include the use of a noninflammatory model as results may differ in the presence of an acute inflammatory insult and the inability to measure protein concentrations of inflammatory mediators due to limited synovial fluid sample volume. CONCLUSIONS: Expression relative to baseline, for both inflammatory and matrix genes for up to 42 days post IPA administration, suggests a prolonged effect relative to detection time in both plasma and synovial fluid.