AN ESSENTIAL ROLE FOR INTERLEUKIN-5 AND EOSINOPHILS IN HELMINTH-INDUCED AIRWAY HYPERRESPONSIVENESS

Infection with the parasitic helminth Brugia malayi can result in deve lopment of a severe asthmatic response termed tropical pulmonary eosin ophilia, This disease, thought to result from a host inflammatory resp onse to blood parasites which become trapped in the lung microvasculat ure, is characterized by a profound eosinophilic infiltration into the lungs. Recruitment of eosinophils also correlates with the developmen t of airway hyperresponsiveness (AHR) to cholinergic agonists and seve re asthmatic symptoms. Our studies examined the role of interleukin-5 (IL-5) in helminth-induced pulmonary eosinophilia and AHR. C57BL/6 mic e immunized with killed B, malayi microfilariae and challenged intrave nously with live microfilariae exhibit many of the characteristics of human disease, including peripheral and pulmonary eosinophilia, Cells recovered by bronchoalveolar lavage of sensitized mice consisted of 3. 8% eosinophils on day 1 postchallenge and 84% on day 10, Extracellular major basic protein was present on the surface of airway epithelial c ells as early as day 1 and continued to be evident after 8 days, indic ating sustained activation and degranulation of eosinophils in the lun g. These histologic changes correlated with the development of AHR to carbachol, In contrast to immunocompetent mice, immunization and chall enge with B, malayi in IL-5(-/-) mice did not induce peripheral or pul monary eosinophilia, and these mice failed to show AHR in response to cholinergic agonists. Taken together, these data indicate that IL-5 an d eosinophils are required for the induction of AHR by filarial helmin ths.