Motivala Sarosh J, Dang Jeff, Obradovic Tanja, Meadows Gary G, Butch Anthony W, Irwin Michael R
Cousin Center for Psychoneuroimmunology, University of California-Los Angeles, Neuropsychiatric Institute, 90095-7076, USA.
Alcohol Clin Exp Res. 2003 Nov;27(11):1819-24. doi: 10.1097/01.ALC.0000093741.21492.02.
Basic studies indicate that in vitro and in vivo doses of leptin modulate cellular immune responses. Given evidence that concentrations of leptin are altered in alcoholics who also show immune abnormalities, this study examined the relationships between circulating levels of leptin and markers of cellular and innate immunity.
Circulating levels of leptin, natural killer cell (NK) activity, interleukin-2 (IL-2)-stimulated NK activity, and concanavalin A-stimulated production of IL-2, IL-6, IL-10, and IL-12 were compared between abstinent DSM-IV alcohol-dependent men (n = 27) and age- and gender-matched controls (n = 34).
As compared with controls, alcoholics showed lower NK activity (p < 0.01) and a trend for lower levels of leptin (p = 0.055). In the total sample, leptin predicted NK activity (beta = 0.33; p < 0.05) after controlling for the confounding influence of body mass index, alcohol intake, and smoking. Leptin was not correlated with any of the cytokine measures. To examine whether the effects of leptin were mediated by its direct action on NK, additional studies examined in vitro effects of leptin on NK activity in healthy volunteers (n = 10); leptin doses (0.1, 1, and 10 nM) yielded levels of NK activity comparable to those with media alone.
These data show that circulating levels of leptin are associated with NK activity in humans and suggest that abnormal in vivo concentrations of leptin may contribute to the declines of NK activity in alcoholics who are at risk for infectious diseases.
基础研究表明,体外和体内的瘦素剂量可调节细胞免疫反应。鉴于有证据表明,同时存在免疫异常的酗酒者体内瘦素浓度会发生改变,本研究调查了循环瘦素水平与细胞免疫和先天免疫标志物之间的关系。
比较了戒酒的DSM-IV酒精依赖男性(n = 27)与年龄和性别匹配的对照组(n = 34)之间的循环瘦素水平、自然杀伤细胞(NK)活性、白细胞介素-2(IL-2)刺激的NK活性,以及伴刀豆球蛋白A刺激的IL-2、IL-6、IL-10和IL-12的产生。
与对照组相比,酗酒者的NK活性较低(p < 0.01),瘦素水平也有降低趋势(p = 0.055)。在整个样本中,在控制了体重指数、酒精摄入量和吸烟的混杂影响后,瘦素可预测NK活性(β = 0.33;p < 0.05)。瘦素与任何细胞因子指标均无相关性。为了研究瘦素的作用是否通过其对NK的直接作用介导,另外的研究检测了瘦素对健康志愿者(n = 10)NK活性的体外影响;瘦素剂量(0.1、1和10 nM)产生的NK活性水平与单独使用培养基时相当。
这些数据表明,循环瘦素水平与人类NK活性相关,并提示体内瘦素浓度异常可能导致有感染性疾病风险的酗酒者NK活性下降。