Abbreviations: IFN = interferon; IL = interleukin; Th = T helper
In human patients, asthma frequently is associated with mixed T helper (Th) cell responses. Th2 and Th1 cytokines (eg, interleukin [IL]-13 and interferon [IFN]-[gamma]) can be detected in the lungs simultaneously. However, very little is known about critical mediators for the pathologic and physiologic changes that are induced by mixed T-cell responses in the lungs. Furthermore, IFN-[gamma] has been reported to inhibit or promote Th2-induced lung injury.
To address this controversy, we examined an asthma model induced by mixed Th cell responses. IL-13 was a partial mediator of airway hyperreactivity and goblet cell hyperplasia, while effects on inflammation could not be detected. In contrast, IL-13 was critical for airway physiologic changes and inflammation in a Th2-induced asthma model that was examined in parallel, as has been reported before. In order to address whether the simultaneous presence of IL-13 and IFN-[gamma] had altered the responses in the lungs of the mice that had mixed T-cell responses to the antigen, wild-type mice were given recombinant cytokines intranasally. IFN-[gamma] inhibited IL-13-induced goblet cell hyperplasia as well as the accumulation of eosinophils and neutrophils in BAL fluid. At the same time, when compared to single cytokines IFN-[gamma] and IL-13 potentiated peribronchial, perivascular, and alveolar inflammation, IL-6 levels, and the numbers of natural killer and antigen-presenting cells in the BAL fluid.
Because of the dual effects of IL-13 and IFN-[gamma] in the lungs, it is likely that additional inflammatory mediators are differentially regulated. To further address this important question, this highly standardized model will be analyzed by gene expression microarrays.
* From the Department of Pathology (Dr. Grunig), Columbia University, New York, NY; the Harlem Lung Center (Dr. Ford), Columbia University, New York, NY; the Genetics Institute (Dr. Donaldson), Cambridge, MA; the Department of Pathology (Ms. Hansell and Dr. Warnock) and the Lung Biology Center (Dr. Venkayya), the Howard Hughes Research Institute (Mr. McArthur), University of California, San Francisco, CA; Veterans Affairs Medical Center (Dr. Kurup), University of Wisconsin, Milwaukee, WI; and the DNAX Research Institute (Dr. Rennick), Palo Alto, CA.
This research was supported by grants from the American Lung Association and the J.P. Mara Center For Diseases of the Lung, the National Institutes of Health (grants (T32 HL07185 and P50HL56385), and Schering-Plough Corporation (DNAX Research Institute).
Correspondence to: Gabriele Grunig, PhD, St. Luke's-Roosevelt Hospital Center, 432 W 58th St, Laboratory 504, New York, NY 10019
COPYRIGHT 2002 American College of Chest Physicians
COPYRIGHT 2002 Gale Group
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