IL-13 induces eosinophil recruitment into the lung by an IL-5-and eotaxin-dependent mechanism

Background: IL-13 induces several characteristic features of asthma, includ ing airway eosinophilia, airway hyperresponsiveness, and mucus overproducti on; however, the mechanisms involved are largely unknown. Objective: We hypothesized that IL-13-induced inflammatory changes in the l ung were dependent in part on IL-5 and eotaxin, two eosinophil-selective cy tokines. Methods: Recombinant murine IL-13 was repeatedly administered to the lung b y intranasal delivery until the characteristic features of asthma developed . To analyze the role of IL-5 and eotaxin, we subjected eotaxin gene-target ed, IL-5 gene-targeted, eotaxin/IL-5-double-deficient, IL-5 transgenic, and wild-type mice, of the Balb/C background to the experimental regime. Results: The induction of IL-13-mediated airway eosinophilia was found to o ccur independently of eosinophilia in the blood or bone marrow, indicating that IL-13-induced airway inflammation is primarily mediated by local effec ts of IL-13 in the lung. Eosinophil recruitment into both the lung tissue a nd bronchoalveolar lavage fluid was markedly attenuated in IL-5-deficient m ice in comparison with wild-type controls. Accordingly, IL-13 delivery to I L-5 transgenic mice resulted in a large increase in airway eosinophils in c omparison with wild-type mice. Interestingly, IL-13-induced eosinophilia in the bronchoalveolar lavage fluid of eotaxin-deficient mice was not impaire d; however, these same mice failed to mount a significant tissue eosinophil ia in response to IL-13. Finally, IL-13-induced mucus production was not af fected by the presence of IL-5 or eotaxin, suggesting that IL-13-induced mu cus secretion is mechanistically dissociated from airway eosinophilia. Conclusion: Selective components of the IL-13-induced asthma phenotype-airw ay eosinophilia but not mucus secretion-are differentially regulated by IL- 5 and eotaxin. IL-5 is required for IL-13 to induce eosinophilia throughout the lung, whereas eotaxin regulates the distribution of airway eosinophils .