Cytokine manipulation in animal models of asthma.
We have developed in C57 Black 6 mice an in vivo model of allergic airway inflammation characterized by the presence of IgE antibodies to an inhaled antigen, peribronchial infiltrates with an increased number of eosinophils, and an increased airway responsiveness to nonantigenic bronchoconstrictor stimuli. In this animal model we have investigated the role of different cytokines in the development of IgE antibodies to inhaled antigen, eosinophilic airway inflammation, and airway hyperresponsiveness. The studies were performed by using knockout mice or by exogenous administration of cytokines or cytokine antagonists. Interleukin-4 (IL-4) knockout mice were unable to develop an allergic eosinophilic airway infiltration and did not produce specific IgE antibodies. Chronic aerosol exposure to antigen also did not induce an increase in airway responsiveness. In studies of wild-type mice, pretreatment with the combination of anti-IL5 and anti-IL-5 receptor antibodies, given in an attempt to fully inhibit the effect of endogenously released IL-5, caused a pronounced inhibition of the antigen-induced airway eosinophilia but did not prevent the increase in airway responsiveness. Treatment with IL-12 during the active immunization prevented airway eosinophilia, production of specific IgE antibodies, and the antigen-induced increase in airway responsiveness. In contrast, administration of IL-12 to actively immunized mice during the aerosol exposure abolished airway eosinophilia and airway hyperresponsiveness without affecting the production of specific IgE.
Pauwels
R A
RA
Department of Respiratory Diseases, University Hospital, Ghent, Belgium.
Brusselle
G J
GJ
Kips
J C
JC
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001991:Bronchitis / Q000276:immunology*; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000276:immunology*; D007371:Interferon-gamma / Q000502:physiology*; D018664:Interleukin-12 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D015848:Interleukin-5 / Q000502:physiology; D007378:Interleukins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D015848:Interleukin-5; D007378:Interleukins; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma