Mast Cell Stabilizer Ketotifen Inhibits Gouty Inflammation in Rats.

ABSTRACT

Gout, an extremely painful arthritis with relapsing inflammatory attacks, is a common inflammatory joint disease in adults. We examined the therapeutic effect of ketotifen, a mast cell stabilizer, on monosodium urate (MSU) crystal-induced acute inflammation. Eight-week-old male Wistar rats were injected with MSU crystals (5 mg per rat) into air pouch. Ketotifen (0, 0.1, 03, and 1 mg/kg) was given 1 hour before MSU crystal injection. Lavage histamine, leukocyte counts, mast cell counts, nitric oxide, and proinflammatory mediator levels were assessed 12 hours after MSU injection. Ketotifen significantly inhibited MSU-induced mast cell activation and histamine concentration in air pouch lavage. Ketotifen dose-dependently inhibited MSU-initiated leukocyte infiltration into the air pouch. Furthermore, ketotifen significantly decreased proinflammatory mediators, including nitric oxide, interleukin-1ß, and interleukin-6, production in MSU-treated rats. Ketotifen may attenuate MSU-induced acute inflammation by inhibiting mast cell activation and leukocyte infiltration in rats. Furthermore, ketotifen has the potential to be a new approach in managing patients with gouty inflammation in the future.