Department of Animal Sciences, Rutgers, The State University of New Jersey, Center of Alcohol Studies, New Brunswick, New Jersey 08901, USA.
J Interferon Cytokine Res. 2010 Jan;30(1):15-22. doi: 10.1089/jir.2009.0008.
Chronic alcohol consumption has been shown to decrease the activity of natural killer (NK) cell cytolytic function and the production of various cytokines from the spleen. We have recently shown that naltrexone, an opiate receptor antagonist, when administered for a period of 2 weeks suppresses micro-opiate receptor binding but increases partial differential-opiate receptor activity in rat splenocytes. However, the effects of long-term naltrexone treatment on alcohol-induced alteration of NK cell cytolytic activity and cytokines production in splenocytes have not been determined. Male rats were pair-fed an isocaloric liquid diet or fed an ethanol-containing liquid diet for a period of 3 weeks. These rats were additionally treated after a week with a subcutaneous implant of either a naltrexone pellet or placebo pellet for 2 weeks. Splenocytes were isolated and used for determination of various cytokines interleukin (IL)-2, IL-4, and IL-6, and interferon-gamma (IFN-gamma) using enzyme-linked immunosorbent assay (ELISA), and the basal and IL-2-, IL-12-, or IL-18-induced NK cytolytic activity was measured using a standard 4-h (51)Cr release assay against YAC-1 lymphoma target cells. Ethanol consumption resulted in a reduction of the production of IL-2, IL-4, and IL-6 as well as the basal and cytokine-activated NK cell cytolytic activity and IFN-gamma production in splenocytes. Naltrexone administration increased the production of IL-2, IL-4, and IL-6 and the basal and cytokine-activated NK cell cytolytic activity and IFN-gamma production in the splenocytes of pair-fed and alcohol-fed rats. These results indicated that naltrexone treatment increases NK cell cytolytic activity and cytokine production in the spleen in vivo. Furthermore, these results identify the potential of the use of naltrexone in the treatment of immune deficiency in alcoholic and non-alcoholic patients.
慢性酒精摄入已被证明会降低自然杀伤 (NK) 细胞细胞溶解功能的活性和脾细胞中各种细胞因子的产生。我们最近表明，纳曲酮，一种阿片受体拮抗剂，在给药 2 周内抑制小阿片受体结合，但增加大鼠脾细胞中部分差异阿片受体的活性。然而，长期纳曲酮治疗对酒精引起的 NK 细胞细胞溶解活性和脾细胞中细胞因子产生的改变的影响尚未确定。雄性大鼠用等热量液体饮食或含酒精的液体饮食喂养 3 周。这些大鼠在一周后，用皮下植入纳曲酮丸或安慰剂丸额外治疗 2 周。分离脾细胞，用于测定各种细胞因子白细胞介素 (IL)-2、IL-4 和 IL-6 以及干扰素-γ (IFN-γ)，使用酶联免疫吸附测定 (ELISA)，并使用标准的 4-h (51)Cr 释放测定法测定基础和 IL-2、IL-12 或 IL-18 诱导的 NK 细胞溶解活性针对 YAC-1 淋巴瘤靶细胞。酒精摄入导致脾细胞中 IL-2、IL-4 和 IL-6 的产生以及基础和细胞因子激活的 NK 细胞溶解活性和 IFN-γ产生减少。纳曲酮给药增加了配对喂养和酒精喂养大鼠脾细胞中 IL-2、IL-4 和 IL-6 的产生以及基础和细胞因子激活的 NK 细胞溶解活性和 IFN-γ产生。这些结果表明，纳曲酮治疗可增加体内 NK 细胞溶解活性和脾细胞中细胞因子的产生。此外，这些结果表明纳曲酮在治疗酒精性和非酒精性患者的免疫缺陷方面具有潜在用途。
