Cytokines produced by T-lymphocytes may have significant roles in the
airway inflammation seen in bronchial asthma. Gamma interferon IFN-gam
ma), a T-cell derived cytokine, is known to modify functions of both i
mmune and non-immune cells. In this study, we investigated whether IFN
-gamma can modify guinea pig airway functions in vivo. The isometric t
ension of guinea pig airway strips was measured in a tissue bath fille
d with Krebs-Henseleit solution. Contracting responses to carbachol an
d KCl, and the relaxing response to isoproterenol (ISO) were examined.
Effects of IFN-gamma were examined by comparing responses of the stri
ps incubated with or without IFN-gamma (1000 U.ml(-1); 25,000 U.ml(-1)
. Contracting responses to carbachol and KCl were not affected by the
incubation with IFN-gamma other than slight increased in maximum contr
action by carbachol after 5 hours incubation with 25,000 U.ml(-1) of I
FN-gamma. Both 1 and 5 h incubation of strips with 25,000 U.ml(-1) IFN
-gamma significantly increased the sensitivity to ISO (p < 0.01 and p
< 0.05, respectively) without affecting maximum relaxation. The effect
of IFN-gamma on ISO relaxation was abolished by the denudation of air
way epithelium from strips, indomethacin (2 mu M), and cycloheximide (
70 mu M) but not by N infinity-nitro-L-arginine methyl ester (30 mu M)
. In addition, heat-inactivated INF-gamma and bacterial endotoxin (LPS
, 0.625 pg.ml(-1) had no effect on ISO relaxation. These results sugge
st that IFN-gamma is able to modify airway smooth muscle response to b
eta-adrenergic agonist by inducing release of prostanoids from airway
epithelium.