Gamma-interferon modifies guinea pig airway functions in vitro.
Cytokines produced by T-lymphocytes may have significant roles in the airway inflammation seen in bronchial asthma. Gamma interferon (IFN-gamma), a T-cell derived cytokine, is known to modify functions of both immune and non-immune cells. In this study, we investigated whether IFN-gamma can modify guinea pig airway functions in vitro. The isometric tension of guinea pig airway strips was measured in a tissue bath filled with Krebs-Henseleit solution. Contracting responses to carbachol and KCl, and the relaxing response to isoproterenol (ISO) were examined. Effects of IFN-gamma were examined by comparing responses of the strips 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 contraction by carbachol after 5 hours incubation with 25,000 U.ml-1 of IFN-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 airway epithelium from strips, indomethacin (2 microM), and cycloheximide (70 microM) but not by N omega-nitro-L-arginine methyl ester (30 microM). In addition, heat-inactivated IFN-gamma and bacterial endotoxin (LPS, 0.625 pg.ml-1) had no effect on ISO relaxation. These results suggest that IFN-gamma is able to modify airway smooth muscle response to beta-adrenergic agonist by inducing release of prostanoids from airway epithelium.
Chen
H
H
First Department of Medicine, School of Medicine, Hokkaido University, Sapporo, Japan.
Munakata
M
M
Amishima
M
M
Ukita
H
H
Masaki
Y
Y
Homma
Y
Y
Kawakami
Y
Y
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D019335:Nitroarginine; D011189:Potassium Chloride / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D014132:Trachea / Q000187:drug effects*
D011453:Prostaglandins; D019335:Nitroarginine; D011189:Potassium Chloride; D007371:Interferon-gamma; D002217:Carbachol; D001120:Arginine; D003513:Cycloheximide; D007545:Isoproterenol; D007213:Indomethacin