Iwamoto I, Kumano K, Kasai M, Kurasawa K, Nakao A
Department of Internal Medicine, Chiba University School of Medicine, Japan.
Am J Respir Crit Care Med. 1996 Nov;154(5):1257-60. doi: 10.1164/ajrccm.154.5.8912732.
Interleukin-12 (IL-12) is a key cytokine that promotes Th1-type cell-mediated immunity and inhibits Th2-type responses. We have previously shown that antigen-induced eosinophil recruitment into the airways of sensitized mice is mediated by Th2-type CD4+ T cells that produce IL-5. Therefore, to determine whether IL-12 regulates antigen-induced eosinophil recruitment into the airways, we studied the effect of recombinant murine IL-12 on antigen-induced eosinophil infiltration into the tracheas of sensitized mice, and also the effect of IL-12 on IL-5 and interferon-gamma (IFN-gamma) levels in bronchoalveolar lavage fluid (BALF) from the mice. The intraperitoneal administration of recombinant IL-12 (rIL-12) inhibited antigen-induced eosinophil infiltration into the mouse trachea in a dose-dependent manner. The administration of rIL-12 suppressed IL-5 levels but enhanced IFN-gamma levels in the BALF of the mice after antigen inhalation. The administration of rIL-12 also decreased in vitro antigen-induced IL-4 and IL-5 production, but not IFN-gamma production, in spleen cells of the mice. Furthermore, pretreatment with anti-IFN-gamma monoclonal antibody prevented the IL-12 inhibition of antigen-induced eosinophil infiltration into the tracheas of the mice. These results indicate that IL-12 downregulates antigen-induced eosinophil recruitment into the airways by inhibiting IL-5 production in sensitized animals.
白细胞介素-12（IL-12）是一种关键的细胞因子，可促进Th1型细胞介导的免疫反应并抑制Th2型反应。我们之前已经表明，抗原诱导的嗜酸性粒细胞募集到致敏小鼠的气道中是由产生IL-5的Th2型CD4 + T细胞介导的。因此，为了确定IL-12是否调节抗原诱导的嗜酸性粒细胞募集到气道中，我们研究了重组鼠IL-12对致敏小鼠气管中抗原诱导的嗜酸性粒细胞浸润的影响，以及IL-12对小鼠支气管肺泡灌洗液（BALF）中IL-5和干扰素-γ（IFN-γ）水平的影响。腹腔注射重组IL-12（rIL-12）以剂量依赖的方式抑制抗原诱导的嗜酸性粒细胞浸润到小鼠气管中。吸入抗原后，rIL-12的给药抑制了小鼠BALF中的IL-5水平，但提高了IFN-γ水平。rIL-12的给药还降低了小鼠脾细胞中体外抗原诱导的IL-4和IL-5产生，但不影响IFN-γ的产生。此外，用抗IFN-γ单克隆抗体预处理可防止IL-12对抗原诱导的嗜酸性粒细胞浸润到小鼠气管中的抑制作用。这些结果表明，IL-12通过抑制致敏动物中IL-5的产生来下调抗原诱导的嗜酸性粒细胞募集到气道中。
