Effect of interferon-gamma on allergic airway responses in interferon-gamma-deficient mice.
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-gammaKO) mice. Sensitized mice (IFN-gammaKO 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-gammaKO 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-gammaKO 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.
Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, 50 Charlton Avenue East, Hamilton, Ontario, L8N 4A6 Canada.
Makoto
M
Yoshida
Richard
R
Leigh
Koichiro
K
Matsumoto
Jennifer
J
Wattie
Russ
R
Ellis
Paul M
PM
O'Byrne
Mark D
MD
Inman
D000402:Airway Obstruction; D000818:Animals; D000835:Animals, Wild / Q000276:immunology; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D016535:Bronchial Hyperreactivity / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D001985:Bronchial Provocation Tests / Q000379:methods; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016516:CD4-CD8 Ratio; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D007249:Inflammation; D007371:Interferon-gamma / Q000172:deficiency* / Q000276:immunology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin
D007371:Interferon-gamma; D010047:Ovalbumin