In vivo effects of meloxicam on inflammatory mediators, MMP activity and cartilage biomarkers in equine joints with acute synovitis

Authors: 
de Grauw, J.C.; van de Lest, C. H. A.; Brama, P.A.J.; Rambags, B.P.B.; van Weeren, P. R.
Volume: 
41
Number: 
7
Pages: 
693-699(7)
Journal: 
Equine Veterinary Journal
Date: 
September 2009

Reasons for performing study: Meloxicam is a commonly used nonsteroidal anti-inflammatory drug in equine practice, but little is known about its in vivo effects on joint inflammation and cartilage turnover.

Objectives: To study the effects of meloxicam on biomarkers of inflammation, matrix metalloproteinase (MMP) activity, and cartilage biomarkers in joints with experimental synovitis.

Methods: In a 2-period cross-over study, synovitis was induced at T = 0 h in the L or R intercarpal joint of 6 horses by intraarticular injection of 0.5 ng lipopolysaccharide (LPS). Horses received once daily meloxicam (0.6 mg/kg bwt per os) or placebo starting at post injection hour (PIH) 2, and clinical evaluations as well as blood and synovial fluid (SF) sampling were performed at PIH 0, 8, 24 and 168. Synovial fluid was analysed for prostaglandin E2, bradykinin, substance P, general MMP activity, glycosaminoglycans (GAG), CS846 epitope, type II collagen cleavage fragments (C2C) and type II collagen carboxypropeptide (CPII). Concentrations in meloxicam- vs. placebo-treated joints over time were compared using a linear mixed model.

Results: Lipopolysaccharide injection caused marked transient synovitis without systemic effects. Meloxicam caused a significant reduction in lameness at PIH 8 and 24 and tended to reduce effusion. In addition, meloxicam significantly suppressed SF prostaglandin E2 and substance P release at PIH 8 and bradykinin at PIH 24 compared to placebo treatment. General MMP activity at PIH 8 and 24 was significantly lower in meloxicam- vs. placebo-treated joints, as were GAG, C2C and CPII concentrations at PIH 24.

Conclusions: Acute transient synovitis leads to substantial increases in SF biomarkers of inflammation, MMP activity and cartilage turnover, which can be significantly suppressed by meloxicam.

Potential relevance: Early oral treatment with meloxicam ameliorates not only clinical signs and joint inflammation in acute synovitis, but may also limit inflammation-induced cartilage catabolism.