Matsumoto Atsuhiro, Ohta Noriyuki, Goto Yukiko, Kashiwa Yozo, Yamamoto Shunsuke, Fujino Yuji
From the *Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; and †Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Anesth Analg. 2015 Apr;120(4):895-902. doi: 10.1213/ANE.0000000000000606.
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.
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 ΙІ 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-γ in the culture supernatants. We also assessed the in vivo effects of haloperidol on hapten-induced contact hypersensitivity responses.
Haloperidol inhibited the expression of CD80, CD86, major histocompatibility complex class ΙІ, 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 CD8α) and DCs, haloperidol-treated DCs suppressed the proliferation of allogeneic T cells and effectively inhibited the production of interferon-γ. 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.
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.
氟哌啶醇用于治疗精神分裂症患者时具有免疫调节作用，也用于重症监护病房中使重症患者镇静。尽管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树突状细胞（DC）的功能。DC是强大的抗原呈递细胞，可影响T淋巴细胞的激活和成熟。在本研究中，我们调查了氟哌啶醇对DC介导的免疫反应的体外和体内免疫调节作用。
在细胞培养中使用骨髓来源的DC，我们评估了氟哌啶醇对共刺激分子（CD80和CD86）、主要组织相容性复合体Ⅱ类分子以及DC成熟标志物CD83表达的影响。还评估了DC培养上清液中的白细胞介素-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对半抗原诱导的接触性超敏反应的体内作用。
氟哌啶醇抑制DC上CD80、CD86、主要组织相容性复合体Ⅱ类和CD83分子的表达以及DC培养上清液中白细胞介素-12p40的分泌。在同时含有T细胞（CD4和CD8α）和DC的混合细胞培养物中，经氟哌啶醇处理的DC抑制同种异体T细胞的增殖并有效抑制干扰素-γ的产生。在体内，氟哌啶醇降低了半抗原诱导的接触性超敏反应。此外，D2样受体拮抗剂以类似于氟哌啶醇的方式抑制DC的成熟。
我们的研究结果表明，氟哌啶醇抑制DC的功能成熟，并在抑制整个动物中DC诱导的辅助性T细胞1免疫反应中起重要作用。此外，氟哌啶醇对DC的作用可能由多巴胺D2样受体介导。总之，这些结果表明给予氟哌啶醇可抑制DC介导的免疫反应。
