Haloperidol Suppresses Murine Dendritic Cell Maturation and Priming of the T Helper 1-Type Immune Response
Haloperidol Suppresses Murine Dendritic Cell Maturation and Priming of the T Helper 1-Type Immune Response
复制标题
DOI：
10.1213/ane.0000000000000606
复制
发表时间：
2015-04-01
影响因子：
5.7
通讯作者：
Fujino, Yuji
中科院分区：
文献类型：
--
作者：
Matsumoto, Atsuhiro;Ohta, Noriyuki;Fujino, Yuji
背景：氟哌啶醇用于治疗脑卒中患者时具有免疫调节作用。精神分裂症，也被用来镇静重症监护病房的危重病人。虽然氟哌啶醇影响免疫功能的机制尚不清楚，但一种可能性是它改变了树突状细胞（DC）的功能。DC是影响T淋巴细胞活化和成熟的有效抗原呈递细胞。在这项研究中，我们研究了在体外和体内的免疫调节作用氟哌啶醇对DC介导的immunoassociated responses.METHODS：使用骨髓来源的DC细胞培养，我们评估了氟哌啶醇对共刺激分子（CD 80和CD 86），主要组织相容性复合物II类分子，和DC成熟标志物CD 83的表达的影响。还评估DC培养物上清液的白细胞介素-12 p40水平。此外，我们分析了氟哌啶醇对含有DC和淋巴细胞的混合细胞培养物的影响，并测量了培养上清液中干扰素-γ的分泌。我们还评估了氟哌啶醇在体内对半抗原诱导的接触性超敏反应的影响。结果：氟哌啶醇抑制CD 80，CD 86，主要组织相容性复合物II类，和CD 83分子对DC的表达和DC培养上清液中白细胞介素-12p40的分泌。在含有T细胞（CD 4（+）和CD 8 α（+））和DC的混合细胞培养物中，氟哌啶醇处理的DC抑制同种异体T细胞的增殖并有效地抑制干扰素-γ的产生。在体内，氟哌啶醇减少半抗原诱导的接触性超敏反应。此外，D2样受体的拮抗剂抑制的方式类似于氟哌啶醇的成熟的DCs。结论：我们的研究结果表明，氟哌啶醇抑制的功能成熟的DCs，并在抑制DC诱导的T辅助细胞1免疫反应在整个动物中起着重要的作用。氟哌啶醇对DC的作用可能是通过多巴胺D2样受体介导的。总之，这些结果表明氟哌啶醇给药抑制DC介导的免疫应答。
BACKGROUND: Haloperidol has immunomodulatory effects when used to treat patients with. schizophrenia and also is used to sedate critically ill patients in the intensive care unit. Although the mechanism by which haloperidol affects immune function is unclear, one possibility is that it alters dendritic cell (DC) function. DCs are potent antigen-presenting cells that influence the activation and maturation of T lymphocytes. In this study, we investigated the in vitro and in vivo immunomodulatory effects of haloperidol on DC-mediated immune responses.METHODS: Using bone marrow derived DCs in cell culture, we evaluated the effect of haloperidol on expression of costimulatory molecules (CD80 and CD86), major histocompatibility complex class II molecules, and the DC maturation marker CD83. DC culture supernatants also were evaluated for interleukin-12 p40 levels. In addition, we analyzed the effect of haloperidol on a mixed cell culture containing DCs and lymphocytes and measured the secretion of interferon-gamma in the culture supernatants. We also assessed the in vivo effects of haloperidol on hapten-induced contact hypersensitivity responses.RESULTS: Haloperidol inhibited the expression of CD80, CD86, major histocompatibility complex class II, and CD83 molecules on DCs and the secretion of interleukin-12p40 in DC culture supernatants. In mixed cell cultures containing both T cells (CD4(+) and CD8 alpha(+)) and DCs, haloperidol-treated DCs suppressed the proliferation of allogeneic T cells and effectively inhibited the production of interferon-gamma. In vivo, haloperidol reduced hapten-induced contact hypersensitivity responses. Furthermore, an antagonist to D2-like receptor suppressed the maturation of DCs in a manner similar to haloperidol.CONCLUSIONS: The results of our study suggest that haloperidol suppresses the functional maturation of DCs and plays an important role in the inhibition of DC-induced T helper 1 immune responses in the whole animal. Furthermore, the effect of haloperidol on DCs may be mediated by dopamine D2-like receptors. Together, these results demonstrate that administration of haloperidol suppresses DC-mediated immune responses.