Prophylactic Effect of Highly Selective COX-2 Inhibition in Acute Monosodium Urate Crystal Induced Inflammation in the Rat Subcutaneous Air Pouch

SELIM NALBANT, LAN X. CHEN, MARIE S. SIECK, GILDA CLAYBURNE, and H. RALPH SCHUMACHER

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-a 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. (J Rheumatol 2005;32:1762-4)

Key Indexing Terms:

GOUT
COXIB
AIR-POUCH
INFLAMMATION

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From the University of Pennsylvania School of Medicine and the Arthritis Center, VA Medical Center, Philadelphia, Pennsylvania, USA.

Supported by Merck Sharp and Dohme, Inc.

S. Nalbant, MD, Rheumatology Research Fellow, University of Pennsylvania School of Medicine; L.X. Chen, MD, Clinical Assistant Professor, University of Pennsylvania; M.S. Sieck, Laboratory Technician; G. Clayburne, Laboratory Technician; H.R. Schumacher, MD, Professor of Medicine, University of Pennsylvania, Chief of Rheumatology, VA Medical Center.

Address reprint requests to Dr. H.R. Schumacher, VA Medical Center, University & Woodland Aves., Philadelphia, PA 19104-4283, USA. E-mail: schumacr@mail.med.upenn.edu

Accepted for publication April 20, 2005.

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