beta(2)-agonists prevent Th1 development by selective inhibition of interleukin 12
beta(2)-agonists prevent Th1 development by selective inhibition of interleukin 12
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DOI：
10.1172/jci119674
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发表时间：
1997-09-15
影响因子：
15.9
通讯作者：
Sinigaglia, F
中科院分区：
文献类型：
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作者：
PaninaBordignon, P;Mazzeo, D;Sinigaglia, F
白细胞介素12 （IL-12）在免疫系统中发挥核心作用，使免疫反应偏向T辅助1。（Th1）类型响应，其中；其特点是高干扰素γ和低IL-4的产生。在本报告中，我们提供了β(2)激动剂抑制人单核细胞对脂多糖（LPS）和CD40刺激的树突状细胞产生IL-12的证据。抑制IL-12的产生是选择性的，因为单核细胞产生的其他细胞因子不受影响。IL-12抑制依赖于β(2)-肾上腺素能受体刺激，并与细胞内cAMP水平升高相关。结合它们抑制IL-12产生的能力，当在启动新生儿T淋巴细胞时添加β(2)激动剂时，它们抑制th1型细胞的发育，同时促进T辅助2 （Th2）细胞的分化。此外，体内给予治疗剂量的沙丁胺醇导致体外LPS刺激全血淋巴细胞选择性抑制IL-12的产生。这些发现为临床使用β(2)受体激动剂的免疫学后果提供了新的见解，并可能为治疗th1介导的疾病提供新的途径。
Interleukin 12 (IL-12) plays a central role in the immune system by skewing the immune response towards T helper 1. (Th1) type responses which;are characterized by high interferon-gamma and low IL-4 production. In this report we present evidence that beta(2)-agonists inhibit IL-12 production by both human monocytes in response to lipopolysaccharide (LPS) and dendritic cells stimulated via CD40. Inhibition of IL-12 production is selective, as other cytokines produced by monocytes are unaffected. IL-12 inhibition is dependent on beta(2)-adrenoceptor stimulation and correlates with increased levels of intracellular cAMP. In conjunction with their ability to suppress IL-12 production, when beta(2)-agonists are added at priming of neonatal T lymphocytes, they inhibit the development of Th1-type cells, while promoting T helper 2 (Th2) cell differentiation. Further, the in vivo administration of a therapeutic dose of salbutamol results in the selective inhibition of IL-12 production by whole blood lymphocytes stimulated in vitro with LPS. These findings provide new insight into the immunological consequences of the clinical use of beta(2)-agonists and may suggest new approaches for the treatment of Th1-mediated diseases.