Treatment effects of intra-articular triamcinolone acetonide in an equine model of recurrent joint inflammation.

Abstract

Intra-articular triamcinolone acetonide is a widely used treatment for joint inflammation despite limited scientific evidence of its efficacy. To investigate if intra-articular triamcinolone acetonide has sustained anti-inflammatory effects using an equine model of repeated joint inflammation. Randomised controlled experimental study. For three consecutive cycles 2weeks apart, inflammation was induced in both middle carpal joints of eight horses by injecting 0.25ng lipopolysaccharide (LPS). After the first LPS injection only, treatment with 12mg triamcinolone acetonide (TA) followed in one randomly assigned joint, while the contralateral joint was treated with sterile saline (control). Clinical parameters (composite welfare scores, joint effusion, joint circumference) were recorded and synovial fluid samples were analysed for various biomarkers (total protein, WBCC; PGE2 ; CCL2; TNFα; MMP; GAGs; C2C; CPII) at fixed timepoints (post injection hours 0, 8, 24, 72 and 168). The effects of time and treatment on clinical and synovial fluid parameters and the presence of time-treatment interactions were tested using a linear mixed model for repeated measures with horse as a random effect, and time and treatment as fixed effects. The TA treated joints showed significantly higher peak synovial GAG concentrations (Difference in means 283.1875µg/mL, 95% CI 179.8, 386.6, P<0.000), and PGE2 levels (Difference in means 77.8025pg/mL, 95% CI 21.2, 134.4, P<0.007) after the first inflammation induction. Significantly lower TP levels were seen with TA treatment after the second induction (Difference in means -7.5g/L, 95% CI -14.8, -0.20, P<0.04) . Significantly lower WBCC levels were noted with TA treatment after the first (Difference in means -23.7125×109 cells/L, 95% CI -46.7, -0.7, P<0.04) and second (Difference in means -35.95×109 cells/L, 95% CI -59.0, -12.9, P<0.002) inflammation inductions. Significantly lower general MMP activity was also seen with TA treatment after the second inflammation inductions (Difference in means -51.65 RFU/s, 95% CI -92.4, -10.9, P<0.01). This experimental study cannot fully reflect natural joint disease. In this model, intra-articular TA seems to have some anti-inflammatory activity (demonstrated by reductions in TP, WBCC and general MMP activity) up to 2weeks post treatment but not at 4weeks. This anti-inflammatory effect appeared to outlast a shorter-lived, potentially detrimental effect illustrated by increased synovial GAG and PGE2 levels after the first induction.