Prophylactic effect of highly selective COX-2 inhibition in acute monosodium urate crystal induced inflammation in the rat subcutaneous air pouch.

Abstract

OBJECTIVE: To examine the ability of rofecoxib prophylaxis to blunt the effect of monosodium urate (MSU) crystal inflammation induced in the rat subcutaneous air pouch. METHODS: Eight rats were used in each of 4 groups. On day one, air was injected subcutaneously to create the pouches and gavage feedings were started with placebo or 2 different doses of rofecoxib. Six days later MSU crystals or saline were injected into the pouches. Twenty-four hours later, rats were examined, sacrificed, and pouch fluid studied. RESULTS: Rofecoxib 15 or 30 mg/kg given for 6 days before MSU crystal injection into rat air pouches significantly suppressed the inflammation following injection of 10 mg crystals (p = 0.001) and tended to suppress the milder inflammation induced by 5 mg MSU. Greater effects on phagocytosis were seen with 30 mg/kg rofecoxib. Tumor necrosis factor-alpha levels in pouch fluid measured by ELISA were not suppressed by the rofecoxib. CONCLUSION: Prophylactic use of this cyclooxygenase 2 (COX-2) selective inhibitor in this pilot study suppressed acute MSU crystal induced inflammation. Effects on cytokines need further investigation. COX-2 inhibitors deserve consideration for prophylactic use in interim gout.