title: IL-13 induces eosinophil recruitment into the lung by an IL-5- and eotaxin-dependent mechanism.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pulmonary Medicine, Allergy and Clinical Immunology, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Pope
authors.forename: E B
authors.initials: EB
authors.lastname: Brandt
authors.forename: A
authors.initials: A
authors.lastname: Mishra
authors.forename: S P
authors.initials: SP
authors.lastname: Hogan
authors.forename: N
authors.initials: N
authors.lastname: Zimmermann
authors.forename: K I
authors.initials: KI
authors.lastname: Matthaei
authors.forename: P S
authors.initials: PS
authors.lastname: Foster
authors.forename: M E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000818:Animals; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018793:Interleukin-13 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009093:Mucus / Q000378:metabolism; D011657:Pulmonary Eosinophilia / Q000139:chemically induced*
chemical_list: C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D018793:Interleukin-13; D015848:Interleukin-5