title: IL-4 induces IL-13-independent allergic airway inflammation.
abstract: BACKGROUND
  The related T(H)2 cytokines IL-4 and IL-13 are produced during allergic responses, signal through receptors that contain IL-4 receptor (IL-4R) alpha, and promote allergic inflammation by activating signal transducer and activator of transcription 6. IL-4 promotes T(H)2 response induction, and IL-13 is necessary and sufficient to induce airways hyperresponsiveness (AHR) and goblet cell hyperplasia in some mouse models of asthma. The nonredundant role of IL-13 could reflect unique IL-13 activation of a signaling pathway, inhibitory effects induced by IL-4 but not IL-13, or greater production-potency of IL-13 than IL-4.
  
  
  OBJECTIVE
  We sought to distinguish among these possibilities by determining whether IL-4 inhalation can induce acute allergic airways disease in the absence of IL-13.
  
  
  METHODS
  Mice were inoculated intratracheally with IL-13 or a long-acting formulation of IL-4. Responses of IL-13-deficient and IL-13-sufficient mice were compared, as were responses in mice treated with a potent IL-13 antagonist, anti-IL-4Ralpha antibody, or control reagents.
  
  
  RESULTS
  IL-4 inhalation stimulated bronchoalveolar lavage fluid eosinophilia, AHR, and goblet cell hyperplasia. These responses were similar in IL-13-deficient and IL-13-sufficient mice and were not inhibited by an IL-13 antagonist but were blocked by anti-IL-4Ralpha antibody.
  
  
  CONCLUSIONS
  IL-4 can induce IL-13-independent AHR and goblet cell hyperplasia. Thus the greater role for IL-13 than IL-4 in the induction of these acute allergy-related changes reflects increased production, potency, or both of IL-13 relative to IL-4 rather than a unique IL-13-signaling pathway or a suppressive effect of IL-4.
  
  
  CONCLUSIONS
  Dual IL-4/IL-13 inhibition might be more effective than selective IL-13 inhibition at suppressing allergic inflammation in some circumstances.
authors.affiliation: Division of Immunology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Perkins
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004802:Eosinophilia / Q000139:chemically induced; D005260:Female; D020397:Goblet Cells / Q000187:drug effects* / Q000473:pathology; D006965:Hyperplasia; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology*; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011014:Pneumonia; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced*
chemical_list: D000911:Antibodies, Monoclonal; D007141:Immunoglobulin Fc Fragments; D018793:Interleukin-13; D011993:Recombinant Fusion Proteins; D016210:Methacholine Chloride; D015847:Interleukin-4