Role of IFN-gamma in the inhibition of the allergic airway inflammation caused by IL-12.
T-helper 2 (Th2)-like cells are thought to play a crucial role in the pathogenesis of the eosinophilic airway inflammation observed in asthma. In a murine model of allergen-induced airway eosinophilia and bronchial hyperresponsiveness (BHR), we have shown that interleukin (IL)-12 can suppress antigen-induced airway changes despite the presence of circulating specific IgE. In the present study, we investigated the role of interferon-gamma (IFN-gamma) in the inhibitory effects of IL-12 on allergic airway inflammation. Repeated daily exposure of actively immunized mice to aerosolized ovalbumin (OVA), as compared with aerosolized saline (SAL), induced a significant increase in bronchoalveolar lavage fluid (BALF) eosinophilia and OVA-specific serum IgE in both IFN-gamma-receptor-deficient (IFN-gammaR KO) and wild-type mice. As compared with placebo (PLAC), administration of recombinant murine IL-12 (rmIL-12) during the daily aerosol exposure (but not at the time of immunization) significantly inhibited BALF eosinophilia in both IFN-gammaR KO mice and wild-type controls, without influencing the production of specific IgE. In contrast, administration of rmIL-12 during the active immunization inhibited both BALF eosinophilia and specific IgE in wild-type mice as compared with littermates given PLAC; however, treatment with rmIL-12 during immunization, in comparison with PLAC, caused a significant increase in BALF eosinophilia and specific IgE in IFN-gammaR KO mice. These results demonstrate that inhibition of the allergen-induced eosinophil influx in murine airways by IL-12 is IFN-gamma-dependent during the initial sensitization, but becomes IFN-gamma-independent during the secondary response.
Bruselle
G G
GG
Department of Respiratory Diseases, University Hospital Ghent, Belgium.
Kips
J C
JC
Peleman
R A
RA
Joos
G F
GF
Devos
R R
RR
Tavernier
J H
JH
Pauwels
R A
RA
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003433:Crosses, Genetic; D007371:Interferon-gamma / Q000502:physiology*; D018664:Interleukin-12 / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000633:toxicity; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma