J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/03/1089/12 $2.00
Volume 185, Number 6, March 17, 1997 1089-1100

Interleukin-10 Is a Natural Suppressor of Cytokine Production and Inflammation in a Murine Model of Allergic Bronchopulmonary Aspergillosis

By Gabriele Grünig,^* David B. Corry, Michael W. Leach,^§ Brian W.P. Seymour,^* Viswanath P. Kurup, and Donna M. Rennick^*

From the ^* Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304;  Department of Medicine, University of California, San Francisco, California 94110; ^§ Schering-Plough Research Institute, Lafayette, New Jersey 07848; and the  Department of Medicine, Allergy Immunology Division, Medical College of Wisconsin and Research Service, Veterans' Administration Medical Center, Milwaukee, Wisconsin 53295

We have used interleukin-10 (IL-10) gene knockout mice (IL-10^/) to examine the role of endogenous IL-10 in allergic lung responses to Aspergillus fumigatus Ag. In vitro restimulated lung cells from sensitized IL-10^/ mice produced exaggerated amounts of IL-4, IL-5, and interferon- (IFN-) compared with wild-type (WT) lung cells. In vivo, the significance of IL-10 in regulating responses to repeated A. fumigatus inhalation was strikingly revealed in IL-10^/ outbred mice that had a 50-60% mortality rate, while mortality was rare in similarly treated WT mice. Furthermore, IL-10^/ outbred mice exhibited exaggerated airway inflammation and heightened levels of IL-5 and IFN- in bronchoalveolar lavage (BAL) fluids. In contrast, the magnitude of the allergic lung response was similar in intranasally (i.n.) sensitized IL-10^/ and wild-type mice from a different strain (C57BL/6). Using a different route of priming (intraperitoneal) followed by one i.n. challenge we found that IL-10^/ C57BL/6 mice had heightened eosinophilic airway inflammation, BAL-IL-5 levels, and numbers of T cells in the lung tissues compared with WT mice. We conclude that IL-10 can suppress inflammatory Th2-like lung responses as well as Th1-like responses given the constraints of genetic background and route of priming.

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