Histamine potently suppresses human IL-12 and stimulates IL-10 production via H2 receptors.
Histamine potently suppresses human IL-12 and stimulates IL-10 production via H2 receptors.
复制标题
组胺可有效抑制人 IL-12 并通过 H2 受体刺激 IL-10 的产生。
作者：
I. Elenkov;E. Webster;D. Papanicolaou;T. Fleisher;G. Chrousos;R. Wilder
IL-12和IL-10分别刺激Th 1和Th 2免疫应答。一些过敏反应、感染和肿瘤的发生与组胺过量产生和向Th 2反应的转变有关。在这里，我们解决的可能性，这种关联是因果关系，至少部分地，调节IL-12和IL-10的生产组胺。我们报告，组胺剂量依赖性地抑制分泌的人IL-12（p70）和增加生产的IL-10在LPS刺激的全血培养。组胺的这些作用被H2受体拮抗剂西咪替丁拮抗，但不是由选择性H1和H3受体阻滞剂，并模仿H2受体激动剂。组胺对IL-12和IL-10分泌的影响不依赖于内源性IL-10分泌或外源性IL-12的加入，而磷酸二酯酶抑制剂Ro 20-1724增强组胺对IL-12和IL-10产生的影响，其作用涉及cAMP。组胺对IL-12和IL-10产生的类似调节作用，可被H2拮抗剂西咪替丁逆转，分别在金黄色葡萄球菌科万菌株1和LPS刺激的PBMC和分离的单核细胞中观察到。因此，组胺通过刺激外周血单核细胞上的H2受体和随后的cAMP升高，抑制IL-12并刺激IL-10分泌，这种变化可能导致Th 1/Th 2平衡向Th 2优势的转变。这可能代表了一种新的机制，通过这种机制，组胺的过度分泌增强了Th 2介导的过敏反应，并有助于某些感染和肿瘤的发展，这些感染和肿瘤通常由Th 1依赖性免疫机制消除。
IL-12 and IL-10, respectively, stimulate Th1 and Th2 immune responses. The development of some allergic reactions, infections, and tumors are associated with excessive histamine production and a shift toward Th2 responses. Here we address the possibility that this association is causally linked, at least in part, to modulation of IL-12 and IL-10 production by histamine. We report that histamine dose-dependently inhibited the secretion of human IL-12 (p70) and increased the production of IL-10 in LPS-stimulated whole blood cultures. These effects of histamine were antagonized by cimetidine, an H2 receptor antagonist, but not by selective H1 and H3 receptor blockers, and were mimicked by an H2 receptor agonist. The effects of histamine on IL-12 and IL-10 secretion were independent of endogenous secretion of IL-10 or exogenous addition of IL-12, while Ro 20-1724, a phosphodiesterase inhibitor, potentiated the effects of histamine on IL-12 and IL-10 production, implicating cAMP in its actions. Similar modulatory effects of histamine on IL-12 and IL-10 production, which were reversed by the H2 antagonist cimetidine, were observed in PBMC and isolated monocytes stimulated by Staphylococcus aureus Cowan strain 1 and LPS, respectively. Thus, histamine, via stimulation of H2 receptors on peripheral monocytes and subsequent elevation of cAMP, suppresses IL-12 and stimulates IL-10 secretion, changes that may result in a shift of Th1/Th2 balance toward Th2-dominance. This may represent a novel mechanism by which excessive secretion of histamine potentiates Th2-mediated allergic reactions and contributes to the development of certain infections and tumors normally eliminated by Th1-dependent immune mechanisms.
人单核细胞来源的可溶性产物在组胺和刀豆球蛋白 A 诱导的抑制性 T 细胞的生成中具有辅助功能。
DOI：
10.1172/jci110629
发表时间：
1982
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Beer,DJ;Dinarello,CA;Rosenwasser,LJ;Rocklin,RE
通讯作者：
Rocklin,RE
影响因子：
56.9
作者：
Fearon, DT;Locksley, RM
通讯作者：
Locksley, RM