RAPID AND SELECTIVITY INDUCTION OF BLOOD EOSINOPHILIA IN GUINEA-PIGS BY RECOMBINANT HUMAN INTERLEUKIN-5

Interleukin 5 (IL-5) has been implicated as a causal mediator in the d evelopment of pulmonary eosinophilia and airway hyperreactivity in hum an asthma, Supportive evidence for a pathogenic role of IL-5 in this d isease has been provided by guinea pig models in which antigen-induced lung eosinophilia and bronchial hyperresponsiveness have been specifi cally attenuated with a neutralizing antibody to IL-5, In the present report, we describe a rapid mechanism-based model of IL-5-induced eosi nophilia in the guinea pig, Our results show that intravenous injectio n of human IL-5 induced a 5-10-fold increase in the percentage and num ber of eosinophils in blood within 1 hour, In contrast, neutrophils an d mononuclear cells were not recruited during this time, The increase in eosinophils was blocked by pretreatment of animals with an anti-IL5 monoclonal antibody (TRFK5) in doses similar to those which inhibit e osinophilia in guinea pig asthma models. Furthermore, dexamethasone, a potent inhibitor of eosinophilia in guinea pig asthma, profoundly sup pressed the eosinophilia induced by human IL-5. This rapid model will be useful for elucidating the eosinophil activating properties of IL-5 in vivo and may potentially facilitate the development of IL-5 recept or antagonists for the specific blockade of the eosinophilic inflammat ion observed in human asthma.