POTENTIAL ROLE OF INTERLEUKIN-1 IN ALLERGEN-INDUCED LATE ASTHMATIC REACTIONS IN GUINEA-PIGS - SUPPRESSIVE EFFECT OF INTERLEUKIN-1 RECEPTOR ANTAGONIST ON LATE ASTHMATIC REACTION

Interleukin (IL)-1 is a pluripotential proinflammatory cytokine and is thought to be involved in the pathogenesis of bronchial asthma and la te asthmatic reactions (LARs). To determine whether IL-1 plays a role in LAR, guinea pigs sensitized with Ascaris antigen were used. We eval uated IL-1 production by immunostaining with anti-IL-1 beta antibody a nd elucidated the action of IL-1 in LAR with recombinant IL-1 receptor antagonist. Immunostaining revealed that IL-1 beta-like immunoreactiv ity-positive cells increased in the airway walls and in bronchoalveola r lavage fluid after the antigen challenge. IL-1 receptor antagonist p rotein pretreatment reduced the generation of LAR in terms of pulmonar y resistance. IL-1 receptor antagonist protein pretreatment did nor ch ange cellular components but reduced the percentage of hypodense eosin ophils in bronchoalveolar lavage fluid. We also studied the direct eff ect of recombinant human IL-1 beta on pulmonary resistance and eosinop hil activity measured as released eosinophil peroxidase activity. Reco mbinant human IL-1 beta did not change pulmonary resistance but primed eosinophils to release eosinophil peroxidase activity in response to platelet activating factor. Therefore these results suggest that IL-1 was produced in sensitized pulmonary tissue of guinea pigs by allergen exposure and played a role in the generation of LAR, at least partial ly by modulating the activation of eosinophils.