KETOTIFEN, AN ANTIALLERGIC AGENT, SUPPRESSES PULMONARY EOSINOPHILIA INDUCED BY THE NEMATODE NIPPOSTRONGYLUS BRASILIENSIS IN RATS

Certain parasitic infections such as ascariasis and hookworm diseases occasionally cause a type of Dither's syndrome. This syndrome, which consists of transitory and migratory pulmonary infiltration : with eosinophilia, is presumed to be triggered by hypersensitivity reaction. Previously, we showed that infection with the nematode Nippostrongylus brasiliensis induces similar lung lesions, that are markedly enhanced after challenge infection. To examine the role of mast cells in, nematode-induced pneumonitis, N. brasiliensis-primed Brown Norway rats received continuous intravenous administration of the mast cell stabilizer ketotifen (6 mg/day/kg body weight) from one day prior to 3 days after challenge infection.Significantly larger numbers of rat mast cell protease (RMCP) II-positive mast cells were identified in the lungs of ketotifen-administered animals than in saline-perfused animals, suggesting that ketotifen treatment significantly suppressed mast cell activation. Morphological analysis of lung sections showed that ketotifen administration significantly suppressed eosinophil infiltration. Areas of lung granulomas, also triggered by nematode infection, were smaller in ketotifen-treated than in non-treated animals, although this effect was not statistically significant. The worm recoveries from the small intestine did not differ between ketotifen-treated and non-treated animals, indicating that the agent did not hinder lung migration of worms. These results suggest that mast cells play an important role at least in the development of mematode-induced lung eosinophilia.