[Effects of gamma interferon (IFN-gamma) and interleukin-1 beta (IL-1 beta) on contractile and relaxing responses of guinea-pig airway strips].
Gamma interferon (IFN-gamma) and interleukin(IL)-1 beta produced by T lymphocytes and macrophages may have significant roles in the airway inflammation seen in bronchial asthma and are known to modify functions of both immune and non-immune cells. In this study, we examined whether the cytokines can modify contractile and relaxing responses of guinea pig airway strips in vitro. The isometric tension of guinea-pig 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 the cytokines were examined by comparing responses of the strips incubated with or without IFN-gamma (1,000 U/ml, 25,000 U/ml) and IL-1 beta (25 ng/ml, 250 ng/ml). Contracting responses to carbachol and KCl were not affected by the incubation with IFN-gamma but slightly increased in maximum contraction by carbachol after 5 hours incubation with 25,000 U/ml of IFN-gamma. Both 1- and 5-hour incubation of the strips with 250 ng/ml of IL-1 beta significantly decreased the sensitivity to KCl without affecting maximum contraction. 1- and 5-hour incubation of the strips with 25,000 U/ml of IFN-gamma or 250 ng/ml of IL-1 beta significantly increased or decreased the sensitivity to ISO without affecting maximum relaxation, respectively. Denudation of epithelium from the strips completely abolished the effects of the cytokines on KCl and ISO responses. In addition, the effects of IFN-gamma on ISO relaxation and IL-1 beta on KCl contraction were abolished by indomethacin but not by N omega-nitro-L-arginine methyl ester (N omega-NAME). The effect of IL-1 beta on ISO was inhibited both by indomethacin and by N omega-NAME. These results suggest that IFN-gamma and IL-1 beta may modify airway smooth muscle responses through their effects on airway epithelium by inducing the release of prostanoids and/or nitric oxide.
Chen
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First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D053583:Interleukin-1beta; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D014132:Trachea / Q000502:physiology
D007375:Interleukin-1; D053583:Interleukin-1beta; D010446:Peptide Fragments; C052994:interleukin-1beta (163-171); D011189:Potassium Chloride; D007371:Interferon-gamma; D002217:Carbachol; D007545:Isoproterenol