Gg. Brusselle et al., ROLE OF IFN-GAMMA IN THE INHIBITION OF THE ALLERGIC AIRWAY INFLAMMATION CAUSED BY IL-12, American journal of respiratory cell and molecular biology, 17(6), 1997, pp. 767-771
T-helper 2 (Th2)-like cells are thought to play a crucial role in the
pathogenesis of the eosinophilic airway inflammation observed in asthm
a. In a murine model of allergen-induced airway eosinophilia and bronc
hial hyperresponsiveness (BHR), we have shown that interleukin (IL)-12
can suppress antigen-induced airway changes despite the presence of c
irculating specific IgE. In the present study, we investigated the rol
e of interferon-gamma (IFN-gamma) in the inhibitory effects of IL-12 o
n allergic airway inflammation. Repeated daily exposure of actively im
munized mice to aerosolized ovalbumin (OVA), as compared with aerosoli
zed saline (SAL), induced a significant increase in bronchoalveolar la
vage fluid (BALF) eosinophilia and OVA-specific serum IgE in both IFN-
gamma-receptor-deficient (IFN-gamma R KO) and wild-type mice. As compa
red with placebo (PLAC), administration of recombinant murine IL-12 (r
mIL-12) during the daily aerosol exposure (but not at the time of immu
nization) significantly inhibited BALF eosinophilia in both IFN-gamma
R KO mice and wild-type controls, without influencing the production o
f specific IgE. In contrast, administration of rmIL-12 during the acti
ve immunization inhibited both BALF eosinophilia and specific IgE in w
ild-type mice as compared with littermates given PLAC; however, treatm
ent with rmIL-12 during immunization, in comparison with PLAC, caused
a significant increase in BALF eosinophilia and specific IEE in IFN-ga
mma R KO mice. These results demonstrate that inhibition of the allerg
en-induced eosinophil influx in murine airways by IL-12 is IFN-gamma-d
ependent during the initial sensitization, but becomes IFN-gamma-indep
endent during the secondary response.