The effect of suplatast tosilate, which has been proven to inhibit T-cell s
ynthesis 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 ravage and lung fixation. After antigen ch
allenge, all guinea pigs in the vehicle group displayed dual-phase airway o
bstruction 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 airwa
ys were significantly inhibited, but the early asthmatic response was not a
ffected. 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 degranu
lation.