Interleukin-12 prevents antigen-induced eosinophil recruitment into mouse airways
Interleukin-12 prevents antigen-induced eosinophil recruitment into mouse airways
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DOI：
10.1164/ajrccm.154.5.8912732
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发表时间：
1996-11-01
影响因子：
24.7
通讯作者：
Nakao, A
中科院分区：
文献类型：
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作者：
Iwamoto, I;Kumano, K;Nakao, A
白细胞介素-12 (IL-12) 是一种关键细胞因子，可促进 Th1 型细胞介导的免疫并抑制 Th2 型反应。我们之前已经证明，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对抗原诱导的嗜酸性粒细胞浸润致敏小鼠气管的影响，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。腹腔内给予重组IL-12（rIL-12）以剂量依赖性方式抑制抗原诱导的嗜酸性粒细胞浸润小鼠气管。 rIL-12的施用抑制了IL-5水平，但在抗原吸入后增强了小鼠BALF中的IFN-γ水平。 rIL-12的施用还减少了体外抗原诱导的小鼠脾细胞中IL-4和IL-5的产生，但不减少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小鼠气管的抑制。这些结果表明，IL-12 通过抑制致敏动物中 IL-5 的产生，下调抗原诱导的嗜酸性粒细胞募集到气道中。
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.