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

被引:247
作者
Pope, SM
Brandt, EB
Mishra, A
Hogan, SP
Zimmermann, N
Matthaei, KI
Foster, PS
Rothenberg, ME [1 ]
机构
[1] Childrens Hosp, Med Ctr, Dept Pediat, Div Pulm Med Allergy & Clin Immunol, Cincinnati, OH 45229 USA
[2] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA
[3] Australian Natl Univ, John Curtin Sch Med Res, Div Biochem & Mol Biol, Canberra, ACT 2601, Australia
关键词
asthma; allergy; interleukin; chemokine; eotaxin;
D O I
10.1067/mai.2001.118600
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: IL-13 induces several characteristic features of asthma, including airway eosinophilia, airway hyperresponsiveness, and mucus overproduction; however, the mechanisms involved are largely unknown. Objective: We hypothesized that IL-13-induced inflammatory changes in the lung were dependent in part on IL-5 and eotaxin, two eosinophil-selective cytokines. Methods: Recombinant murine IL-13 was repeatedly administered to the lung by intranasal delivery until the characteristic features of asthma developed. To analyze the role of IL-5 and eotaxin, we subjected eotaxin gene-targeted, 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 occur independently of eosinophilia in the blood or bone marrow, indicating that IL-13-induced airway inflammation is primarily mediated by local effects of IL-13 in the lung. Eosinophil recruitment into both the lung tissue and bronchoalveolar lavage fluid was markedly attenuated in IL-5-deficient mice in comparison with wild-type controls. Accordingly, IL-13 delivery to IL-5 transgenic mice resulted in a large increase in airway eosinophils in comparison with wild-type mice. Interestingly, IL-13-induced eosinophilia in the bronchoalveolar lavage fluid of eotaxin-deficient mice was not impaired; however, these same mice failed to mount a significant tissue eosinophilia in response to IL-13. Finally, IL-13-induced mucus production was not affected by the presence of IL-5 or eotaxin, suggesting that IL-13-induced mucus secretion is mechanistically dissociated from airway eosinophilia. Conclusion: Selective components of the IL-13-induced asthma phenotype-airway 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.
引用
收藏
页码:594 / 601
页数:8
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