Interleukin-4 receptor blockade prevents airway responses induced by antigen challenge in mice.
The functional role of interleukin (IL)-4 in the development of airway hyperresponsiveness (AHR) and pulmonary eosinophilia in response to sensitization and challenge of mice with sheep red blood cells (SRBC) was examined. Control- and SRBC-sensitized A/J mice were treated with an antibody to the murine IL-4 receptor (anti-IL-4R) 3 days before intratracheal challenge with the antigen or vehicle only. Blockade of IL-4R significantly reduced antigen-induced AHR and prevented increases in goblet cells and bronchoalveolar lavage (BAL) eosinophils. Treatment with anti-IL-4R did not affect antigen-induced increases in lung mRNA and BAL protein levels of IL-5 and interferon-gamma or IL-4 mRNA but did significantly increase IL-4 protein levels. Antigen-induced AHR was not reduced by treatment with antibodies to the adhesion molecules, vascular cell adhesion molecule-1 and very late activation antigen-4. Administration of IL-4 over a 7-day period did not increase airway reactivity or induce any changes in BAL cell numbers in naive mice. These results demonstrate that IL-4 is necessary for in vivo development of antigen-induced AHR, goblet cell metaplasia, and pulmonary eosinophilia.
Gavett
S H
SH
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205, USA.
O'Hearn
D J
DJ
Karp
C L
CL
Patel
E A
EA
Schofield
B H
BH
Finkelman
F D
FD
Wills-Karp
M
M
D000818:Animals; D018926:Anti-Allergic Agents / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D015703:Antigens, CD / Q000187:drug effects* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors* / Q000187:drug effects* / Q000276:immunology; D019948:Receptors, Interleukin-4; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D011994:Recombinant Proteins; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D018926:Anti-Allergic Agents; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000941:Antigens; D015703:Antigens, CD; D016207:Cytokines; D039041:Integrin alpha4beta1; D016023:Integrins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D015847:Interleukin-4