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可卡因依赖个体的免疫系统炎症:对药物研发的启示

Immune system inflammation in cocaine dependent individuals: implications for medications development.

作者信息

Fox Helen C, D'Sa Carrol, Kimmerling Anne, Siedlarz Kristen M, Tuit Keri L, Stowe Raymond, Sinha Rajita

机构信息

The Connecticut Mental Health Center, Yale University School of Medicine, Department of Psychiatry, New Haven, CT 06519, USA.

出版信息

Hum Psychopharmacol. 2012 Mar;27(2):156-66. doi: 10.1002/hup.1251.

Abstract

OBJECTIVES

Cocaine dependence is a chronic stress state. Furthermore, both stress and substance abuse have robust and reciprocal effects on immune system cytokines, which are known to be powerful modulators of mood. We therefore examine basal and provoked changes in peripheral cytokines in cocaine dependent individuals to better understand their role in the negative reinforcing effects of cocaine.

METHODS

Twenty-eight (16 F/12 M) treatment-seeking cocaine dependent individuals and 27 (14 F/13 M) social drinkers were exposed to three 5-min guided imagery conditions (stress, drug cue, relaxing) presented randomly across consecutive days. Measures of salivary cortisol, tumor necrosis factor alpha (TNFα), interleukin-10 (IL-10), and interleukin-1 receptor antagonist (IL-1ra) were collected at baseline and various post-imagery time-points.

RESULTS

Cocaine abusers demonstrated decreased basal IL-10 compared with social drinkers. They also showed significant elevations in pro-inflammatory TNFα when exposed to stress compared with when they were exposed to relaxing imagery. This was not observed in the social drinkers. Conversely, social drinkers demonstrated increases in the anti-inflammatory markers, IL-10 and IL-1ra, following exposure to cue, which were not seen in the dependent individuals.

CONCLUSIONS

Cocaine dependent individuals demonstrate an elevated inflammatory state both at baseline and following exposure to the stress imagery condition. Cytokines may reflect potentially novel biomarkers in addicted populations for treatment development.

摘要

目的

可卡因依赖是一种慢性应激状态。此外,应激和药物滥用对免疫系统细胞因子具有强大的相互作用,而这些细胞因子是已知的情绪强效调节因子。因此,我们研究可卡因依赖个体外周细胞因子的基础水平和激发后的变化,以更好地理解它们在可卡因负性强化作用中的作用。

方法

28名(16名女性/12名男性)寻求治疗的可卡因依赖个体和27名(14名女性/13名男性)社交饮酒者连续数天随机接受三种5分钟的引导式意象条件(应激、药物线索、放松)。在基线和意象引导后的不同时间点收集唾液皮质醇、肿瘤坏死因子α(TNFα)、白细胞介素-10(IL-10)和白细胞介素-1受体拮抗剂(IL-1ra)的测量值。

结果

与社交饮酒者相比,可卡因滥用者的基础IL-10水平降低。与接触放松意象时相比,他们在接触应激时促炎细胞因子TNFα也显著升高。社交饮酒者未观察到这种情况。相反,社交饮酒者在接触线索后抗炎标志物IL-10和IL-1ra增加,而依赖个体未出现这种情况。

结论

可卡因依赖个体在基线时以及接触应激意象条件后均表现出炎症状态升高。细胞因子可能反映成瘾人群中潜在的新型生物标志物,用于治疗开发。

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