Il-10 gene knockout attenuates allergen-induced airway hyperresponsiveness in
C57bl/6 mice.
Justice, J. Paul, Y. Shibata, S. Sur, J. Mustafa, M. Fan, and M. R. Van Scott.
1Departments of Physiology and Pharmacology, Brody School of Medicine at East
Carolina University, Greenville, North Carolina 27858; and 2Department of Internal
Medicine, University of Texas Medical Branch, Galveston, Texas
APStracts 7:0257L, 2000.
Intratracheal administration of interleukin-10 (IL-10) has been reported to inhibit allergic
inflammation but augment airway hyperresponsiveness (AHR). In the present study,
airway and smooth muscle responsiveness to methacholine (MCh) were compared in
wild-type (WT) and IL-10-deficient (IL-10-KO) mice to investigate the role of
endogenous IL-10 in AHR development. Naive WT and IL-10-KO mice exhibited similar
dose-dependent increases in airway resistance (Raw) to intravenous MCh. Sensitization
and challenge with ragweed (RW) induced a twofold increase in responsiveness to
intravenous MCh in WT mice, but hyperresponsiveness was not observed in similarly
treated IL-10-KO mice. Likewise, tracheal rings from RW-sensitized and challenged WT
mice exhibited a fourfold greater responsiveness to MCh than IL-10-KO tracheal
preparations. Measurements of airway constriction by whole body plethysmography
further supported the Raw and tracheal ring data (i.e., AHR was not observed in the
absence of IL-10). Interestingly, factors previously implicated in the development of
AHR , including IL-4, IL-5, IL-13, IgA, IgG1, IgE, eosinophilia, and lymphocyte
recruitment to the airways, were upregulated in the IL-10-KO mice. Treatment with
recombinant murine IL-10 at the time of allergen challenge reduced the magnitude of
inflammation but reinstated AHR development in IL-10-KO mice. Adoptive transfer of
mononuclear splenocytes to IL-10-sufficient SCID mice indicated that lymphocytes were
an important source of the IL-10 impacting AHR development. These results provide
evidence that IL-10 expression promotes the development of allergen-induced smooth
muscle hyperresponsiveness.
Received 10 February 2000; accepted in final form 19 September 2000
APS Manuscript Number L52-0.
Article publication pending Am J Physiol Lung Cell Mol Physiol
ISSN 1080-4757 Copyright 2000 The American Physiological Society.
Published in APStracts on 30 November 2000