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酒精戒断对慢性酒精使用者单核细胞亚群缺陷的影响。

Effects of alcohol withdrawal on monocyte subset defects in chronic alcohol users.

机构信息

Institut National de la Santé et Recherche Médicale U1183, Institute for Regenerative Medecine and Biotherapies, Saint-Eloi Hospital, Centre Hospitalier Régional Universitaire Montpellier, Montpellier, France;

University of Montpellier, Montpellier, France.

出版信息

J Leukoc Biol. 2016 Nov;100(5):1191-1199. doi: 10.1189/jlb.5A0216-060RR. Epub 2016 Jun 2.

DOI:10.1189/jlb.5A0216-060RR
PMID:27256567
Abstract

Excessive alcohol consumption has a modulating effect on immune functions that may contribute to decreased immunity and host defense. It is associated with increased intestinal permeability to endotoxins that is normalized after 14 d of abstinence. Whether and how blood monocyte subsets are impaired in patients with an AUD and what their evolution is after alcohol withdrawal are the paper's objectives. With the use of flow cytometry, blood monocyte subsets were quantified in AUDs before (n = 40) and 2 wk after (n = 33) alcohol withdrawal and compared with HC donors (n = 20). Expression of TLR2 and TLR4 on monocyte subsets was also quantified. Cytokine response of monocytes was monitored following PGN and LPS stimulation. The CD14CD16 subset was decreased, whereas the CD14CD16 subset was expanded (P < 0.001) in AUD compared with HC. The frequencies of TLR2- and TLR4-expressing monocytes were reduced in AUD compared with HC. Although the basal production of IL-1, IL-6, and TNF by monocytes in AUD was compared with HC, the PGN- and LPS-mediated IL-6 and TNF production was increased in AUD. Frequencies of IL-6-expressing monocytes were higher in AUD than HC. Alcohol withdrawal partially restored the distribution of monocyte subsets and the frequency of IL-6-producing monocytes and increased the frequency of TNF-producing cells in response to LPS and PGN stimulation to levels compared with those in HC. Our findings indicate that chronic alcohol use alters the distribution as well as the phenotypic and functional characteristics of blood monocyte subsets, which are partially restored following 2 wk of alcohol withdrawal.

摘要

过量饮酒对免疫功能有调节作用,可能导致免疫力下降和宿主防御功能降低。它与内毒素对肠道通透性的增加有关,这种增加在戒酒 14 天后恢复正常。患有酒精使用障碍 (AUD) 的患者血液单核细胞亚群是否受损以及在戒酒后它们的变化情况是本文的研究目的。本研究使用流式细胞术在 AUD 患者戒酒前(n = 40)和 2 周后(n = 33)定量检测血液单核细胞亚群,并与健康对照者(n = 20)进行比较。还定量检测了单核细胞亚群上 TLR2 和 TLR4 的表达。监测 PGN 和 LPS 刺激后单核细胞的细胞因子反应。与 HC 相比,AUD 中 CD14CD16 亚群减少,而 CD14CD16 亚群扩张(P < 0.001)。与 HC 相比,AUD 中 TLR2 和 TLR4 表达的单核细胞频率降低。尽管 AUD 中单核细胞的基础 IL-1、IL-6 和 TNF 产生与 HC 相比,但 AUD 中 PGN 和 LPS 介导的 IL-6 和 TNF 产生增加。AUD 中表达 IL-6 的单核细胞频率高于 HC。酒精戒断部分恢复了单核细胞亚群的分布以及 IL-6 产生单核细胞的频率,并增加了 LPS 和 PGN 刺激后产生 TNF 的细胞频率,使其恢复到与 HC 相比的水平。我们的研究结果表明,慢性酒精使用改变了血液单核细胞亚群的分布以及表型和功能特征,在戒酒 2 周后部分恢复。

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