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American Journal of Respiratory and Critical Care Medicine Vol 166. pp. 451-456, (2002)
© 2002 American Thoracic Society

Original Article

Effect of Interferon-{gamma} on Allergic Airway Responses in Interferon-{gamma}–deficient Mice

Makoto Yoshida, Richard Leigh, Koichiro Matsumoto, Jennifer Wattie, Russ Ellis, Paul M. O'Byrne and Mark D. Inman

Firestone Institute for Respiratory Health, Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Correspondence and requests for reprints should be addressed to Dr. Mark D. Inman, Firestone Institute, St. Joseph's Hospital, 50 Charlton Avenue East, Hamilton, ON, L8N 4A6 Canada. E-mail: inmanma{at}mcmaster.ca

Interferon (IFN)-{gamma} reduces airway responses after allergen challenge in mice. The mechanisms of this effect are not clear. These studies investigate whether IFN-{gamma} can reverse prolonged airway responses after allergen challenge in IFN-{gamma}–deficient (IFN-{gamma}KO) mice. Sensitized mice (IFN-{gamma}KO and wild-type [WT]) were challenged with ovalbumin. Airway responsiveness, eosinophils in bronchoalveolar lavage fluid, and lung lymphocyte subsets (CD4+ and CD8+) were measured 24 hours and 8 weeks after challenge. In further experiments, we treated IFN-{gamma}KO mice with recombinant IFN-{gamma} starting 4 weeks after the challenge for 1 week or 4 weeks. Airway responsiveness, bronchoalveolar lavage eosinophils, and lung CD4+ cells were increased 8 weeks after challenge in IFN-{gamma}KO but not WT mice. IFN-{gamma} treatment returned lung CD4+ cell numbers to values obtained in unchallenged mice. One week of IFN-{gamma} treatment also returned airway responsiveness to baseline levels; however, 4-week treatment with IFN-{gamma} failed to decrease airway responsiveness below levels observed in untreated animals. This suggests that IFN-{gamma} plays an essential role in reversing allergen-induced airway inflammation and hyperresponsiveness and that it may have dual actions on the latter. Observations that IFN-{gamma} reverses airway responses, even when administered after challenge, suggests that IFN-{gamma} treatment could control allergic disease, including asthma.

Key Words: asthma • bronchial hyperreactivity • airway inflammation




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