Interleukin-4 receptor blockade prevents airway responses induced
by antigen challenge in mice.
Gavett, Stephen H., Daniel J. O'hearn, Christopher L. Karp, Brian H.
Schofield, Fred D. Finkelman, and Marsha Wills-Karp.
Department of Environmental Health Sciences, Johns Hopkins
University School of Hygiene and Public Health and Department of
Medicine, Johns Hopkins University School of Medicine, Baltimore,
Maryland 21205; and the University of Cincinnati, College of
Medicine, Cincinnati, Ohio 45267
APStracts 3:0182L, 1996.
The functional role of 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; M1) three 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 IFN-[gamma]
or IL-4 mRNA, but did significantly increase IL-4 protein levels.
Antigen-induced AHR was not reduced by treatment with antibodies to
adhesion molecules VCAM-1 and VLA-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.
Received 21 February 1996; accepted in final form 11 October
1996.
APS Manuscript Number L58-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996