Suplatast Tosilate Inhibits Late Response and Airway Inflammation in Sensitized Guinea Pigs

Abstract

The effect of suplatast tosilate, which has been proven to inhibit T-cell synthesis of IL-4 and IL-5, on the response to antigen inhalation challenge was investigated in sensitized guinea pigs. The animals were given an oral dose of 30 or 100 mg/kg of suplatast or vehicle (distilled water) daily for 1 wk before antigen challenge. Measurement of pulmonary resistance for 6 h was followed by bronchoalveolar lavage and lung fixation. After antigen challenge, all guinea pigs in the vehicle group displayed dual-phase airway obstruction and accumulation of eosinophils and lymphocytes in the airways. After 1 wk of treatment with the high dose of suplatast, the late asthmatic response and the recruitment of eosinophils and lymphocytes into the airways were significantly inhibited, but the early asthmatic response was not affected. In situ hybridization revealed that challenge-induced increases in IL-5 mRNA-positive cells in lung tissue were significantly inhibited after treatment. Thus, suplatast inhibited airway obstruction in the late phase by specifically inhibiting the inflammatory process after mast cell degranulation.