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阿片剂依赖女性戒断期间 DRD3 基因型对炎性细胞因子反应的差异影响。

Differential effect of the DRD3 genotype on inflammatory cytokine responses during abstinence in amphetamine-dependent women.

机构信息

Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC; Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.

Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.

出版信息

Psychoneuroendocrinology. 2018 Nov;97:37-46. doi: 10.1016/j.psyneuen.2018.06.023. Epub 2018 Jun 30.

DOI:10.1016/j.psyneuen.2018.06.023
PMID:30005280
Abstract

Amphetamine exposure impacts on innate and adaptive immunity and DRD3 may modulate the effect of amphetamine on the immune response. We assessed the immune-cytokine markers in 72 female patients with amphetamine dependence (AD) at baseline and after 4-week drug abstinence and in 51 healthy women. Multiplex magnetic bead assay was used to measure the plasma cytokine expression level simultaneously in all participants and DRD3 rs6280 polymorphism was genotyped in patients. We demonstrated an increase of the T helper 1 (Th1) cytokines (IL-2), Th2 cytokines (IL-4, IL-5, IL-6 and IL-10) and other cytokines (IL-1β) in the entire AD cohort. A similar cytokine pattern, along with a significantly decreased IL-8 and IL-10 levels was observed after 4-week abstinence. Among AD patients with DRD3 rs6280 TT genotype, the cytokine expression profile was consistent with total AD cohort at baseline and revealed a significant down-regulated plasma level of the Th1, Th2, and other cytokines except for IL-6 after 4-week abstinence. In AD group with DRD3 rs6280 C allele carrier, we found IL-2 level was significantly higher than healthy controls at baseline and remained higher, accompanied with a borderline increase in IL-4, IL-6 and IL-1β levels after 4-week abstinence. Our results suggest that chronic use of amphetamine increased both pro- and anti-inflammatory cytokines in AD patients, indicating the immune imbalance that may persist for 4 weeks or more. Besides, DRD3 rs6280 TT genotype may be associated with favorable recovery in general inflammatory cytokines during period of abstinence.

摘要

苯丙胺暴露会影响先天和适应性免疫,DRD3 可能调节苯丙胺对免疫反应的影响。我们评估了 72 名女性苯丙胺依赖(AD)患者在基线时、4 周戒断后以及 51 名健康女性的免疫细胞因子标志物。采用多重磁珠检测法同时检测所有参与者的血浆细胞因子表达水平,并对患者的 DRD3 rs6280 多态性进行基因分型。我们发现在整个 AD 队列中,辅助性 T 细胞 1(Th1)细胞因子(IL-2)、Th2 细胞因子(IL-4、IL-5、IL-6 和 IL-10)和其他细胞因子(IL-1β)增加。在 4 周戒断后,观察到类似的细胞因子模式,同时 IL-8 和 IL-10 水平显著降低。在携带 DRD3 rs6280 TT 基因型的 AD 患者中,细胞因子表达谱与总 AD 队列在基线时一致,并且在 4 周戒断后,除了 IL-6 之外,Th1、Th2 和其他细胞因子的血浆水平明显下调。在携带 DRD3 rs6280 C 等位基因的 AD 组中,我们发现 IL-2 水平在基线时明显高于健康对照组,并且在 4 周戒断后仍然较高,同时 IL-4、IL-6 和 IL-1β水平呈边界升高。我们的研究结果表明,慢性使用苯丙胺增加了 AD 患者的促炎和抗炎细胞因子,表明免疫失衡可能持续 4 周或更长时间。此外,DRD3 rs6280 TT 基因型可能与戒断期间一般炎症细胞因子的良好恢复有关。

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