Development of airway hyperresponsiveness is dependent on interferon-gamma and independent of eosinophil infiltration.
In this study the role of interleukin (IL)4, IL5, interferon (IFN) gamma, and tumor necrosis factor (TNF) alpha in the development of airway hyperresponsiveness and inflammatory cell infiltration was investigated using a murine model for allergic asthma. Mice were sensitized with ovalbumin and subsequently challenged repeatedly with ovalbumin aerosols. During the challenge period, mice were treated with monoclonal antibodies directed against IL4, IL5, IFN gamma, or TNF alpha. Control antibody-treated mice showed airway hyperresponsiveness to methacholine and the presence of eosinophils in bronchoalveolar lavage (BAL). Treatment with antibodies to IFN gamma completely abolished development of airway hyperresponsiveness in ovalbumin-challenged animals. After treatment with antibodies to TNF alpha, airway hyperresponsiveness in the ovalbumin-challenged animals was partially but not significantly inhibited. Antibodies to IL4 or IL5 did not inhibit airway hyperresponsiveness. The presence of eosinophils in BAL of ovalbumin-challenged mice was completely inhibited after treatment with antibodies to IL5. Treatment with antibodies to IL4, IFN gamma, or TNF alpha had no effect on eosinophilia. Because IFN gamma and IL5 have either an effect on the induction of airway hyperresponsiveness or on the development of eosinophil infiltration, our results suggest that the two phenomena are differentially regulated.
Hessel
E M
EM
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, the Netherlands.
Van Oosterhout
A J
AJ
Van Ark
I
I
Van Esch
B
B
Hofman
G
G
Van Loveren
H
H
Savelkoul
H F
HF
Nijkamp
F P
FP
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000201:enzymology / Q000276:immunology*; D007371:Interferon-gamma / Q000502:physiology*; D008168:Lung / Q000201:enzymology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010544:Peroxidases / Q000378:metabolism
D000336:Aerosols; D000911:Antibodies, Monoclonal; D000941:Antigens; D016085:Bronchoconstrictor Agents; D016207:Cytokines; D016210:Methacholine Chloride; D007371:Interferon-gamma; D010047:Ovalbumin; D047209:Eosinophil Peroxidase; D010544:Peroxidases