SUPLATAST TOSILATE, A NEW-TYPE OF ANTIALLERGIC AGENT, PREVENTS THE EXPRESSION OF AIRWAY HYPERRESPONSIVENESS IN GUINEA-PIGS

Suplatast tosilate (suplatast) is an antiallergic agent capable of dow n-regulating the functions of CD4(+) T cells. We now investigated the effects of suplatast on the antigen-induced airway hyperresponsiveness and the underlying allergic inflammatory response in sensitized guine a pigs. Animals that had been immunized twice by ovalbumin inhalation on day 0 and day 7 developed an increased airway responsiveness agains t inhaled acetylcholine 24 h after the ovalbumin challenge on day 14. Suplatast (10 and 100 mg/kg per day) and ketotifen (10 mg/kg per day) given orally from day 0 to day 14 effectively inhibited the expression of airway hyperresponsiveness. They also inhibited the infiltration o f eosinophils and macrophages into broncho-bronchiolar walls and lumen . Interestingly, suplatast, but not ketotifen, inhibited the infiltrat ion of lymphocytes including CD4(+) T cells. Collectively, these resul ts strongly suggest that suplatast prevents the expression of airway h yperresponsiveness due to the ability to suppress the infiltration of inflammatory cells into lung tissues.