CIRCULATING, BUT NOT LOCAL LUNG, IL-5 IS REQUIRED FOR THE DEVELOPMENTOF ANTIGEN-INDUCED AIRWAYS EOSINOPHILIA

IL-5 is induced locally in the lung and systemically in the circulatio n during allergic airways eosinophilic inflammation both in humans and experimental animals. However, the precise role of local and systemic IL-5 in the development of allergic airways eosinophilia remains to b e elucidated. In our current study, we demonstrate that compared with their LL-5(+/+) counterparts, IL-5(-/-) mice lacked an IL-5 response b oth in the lung and peripheral blood, yet they released similar amount s of IL-4, eotaxin, and MIP-1 alpha in the lung after ovalbumin (OVA) sensitization and challenge. At cellular levels, these mice failed to develop peripheral blood and airways eosinophilia while the responses of lymphocytes, neutrophils, and macrophages remained similar to those in IL-5(+/+) mice. To dissect the relative role of local and systemic IL-5 in this model, we constructed a gene transfer vector expressing murine IL-5. Intramuscular IL-5 gene transfer to OVA-sensitized IL-5(- /-) mice led to raised levels of IL-5 compartmentalized to the circula tion and completely reconstituted airways eosinophilia upon OVA challe nge, which was associated with reconstitution of eosinophilia in the b one marrow and peripheral blood. Significant airways eosinophilia was observed for at least 7 d in these mice. in contrast, intranasal IL-5 gene transfer, when rendered to give rise to a significant but compart mentalized level of transgene protein IL-5 in the lung, was unable to reconstitute airways eosinophilia in OVA-sensitized IL-5(-/-) mice upo n OVA-challenge, which was associated with a lack of eosinophilic resp onses in bone marrow and peripheral blood. Our findings thus provide u nequivocal evidence that circulating but not local lung IL-5 is critic ally required far the development of allergic airways eosinophilia. Th ese findings also provide the rationale for developing strategies to t arget circulating IL-5 and/or its receptors in bone marrow to effectiv ely control asthmatic airways eosinophilia.