Chen H
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 1994 May;69(3):423-33.
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.
T淋巴细胞和巨噬细胞产生的γ干扰素（IFN-γ）和白细胞介素（IL）-1β可能在支气管哮喘患者气道炎症中发挥重要作用，并且已知它们可调节免疫细胞和非免疫细胞的功能。在本研究中，我们检测了这些细胞因子是否能在体外调节豚鼠气道条的收缩和舒张反应。在充满Krebs-Henseleit溶液的组织浴中测量豚鼠气道条的等长张力。检测了对卡巴胆碱和氯化钾的收缩反应以及对异丙肾上腺素（ISO）的舒张反应。通过比较在有或无IFN-γ（1000 U/ml、25000 U/ml）和IL-1β（25 ng/ml、250 ng/ml）情况下孵育的气道条的反应，来检测细胞因子的作用。对卡巴胆碱和氯化钾的收缩反应不受IFN-γ孵育的影响，但在与25000 U/ml的IFN-γ孵育5小时后，卡巴胆碱引起的最大收缩略有增加。用250 ng/ml的IL-1β孵育气道条1小时和5小时均显著降低了对氯化钾的敏感性，但不影响最大收缩。用25000 U/ml的IFN-γ或250 ng/ml的IL-1β孵育气道条1小时和5小时，分别显著增加或降低了对ISO的敏感性，但不影响最大舒张。去除气道条的上皮后，细胞因子对氯化钾和ISO反应的作用完全消失。此外，吲哚美辛可消除IFN-γ对ISO舒张和IL-1β对氯化钾收缩的作用，但Nω-硝基-L-精氨酸甲酯（Nω-NAME）不能消除。吲哚美辛和Nω-NAME均可抑制IL-1β对ISO的作用。这些结果表明，IFN-γ和IL-1β可能通过诱导前列腺素和/或一氧化氮的释放，作用于气道上皮，从而调节气道平滑肌反应。
