Meyers Julie A, Liu Amy Y, McTiernan Anne, Wener Mark H, Wood Brent, Weigle David S, Sorensen Bess, Chen-Levy Zehava, Yasui Yutaka, Boynton Alanna, Potter John D, Ulrich Cornelia M
Department of Epidemiology, University of Washington, Seattle, Washington 98195, USA.
J Endocrinol. 2008 Oct;199(1):51-60. doi: 10.1677/JOE-07-0569. Epub 2008 Jul 9.
Experimental studies and case reports suggest a multifunctional role of leptin in immune function. However, clinical studies of leptin in healthy individuals with a comprehensive assessment of immunity are lacking. This study investigated associations between serum leptin concentrations and multiple biomarkers of cellular immunity and inflammation among 114 healthy postmenopausal, overweight, or obese women. Leptin was measured by RIA. C-reactive protein (CRP) and serum amyloid A (SAA) were measured by nephelometry. Flow cytometry was used to measure natural killer (NK) cell cytotoxicity and to enumerate and phenotype lymphocyte subsets. T-lymphocyte proliferation was assessed in response to phytohemagluttinin, as well as to anti-CD3 antibodies by the flow cytometric cell division tracking method. Multiple linear regression analysis with adjustment for confounding factors and log transformation, where appropriate, was used. Serum leptin concentrations were positively associated with serum CRP, SAA, and interleukin 6 (IL6) (P<0.0001, P=0.01, and P=0.04 respectively), more strongly among women with a body mass index (BMI) <30 kg/m(2). The associations were attenuated after adjustment for measured body composition, yet remained significant for CRP and SAA. No statistically significant associations were observed between leptin and NK cytotoxicity, lymphocyte subpopulations, or T-lymphocyte proliferation. This study fills an important gap in knowledge about the relationship between leptin concentrations and immune function in healthy individuals. Findings support an association between serum leptin and the inflammatory proteins CRP and SAA, which appears to be mediated only partly by adipose tissue. Our study does not support a link between leptin and other immune parameters among overweight or obese, but otherwise healthy postmenopausal women, perhaps because such effects are only present at low or deficient leptin concentrations.
实验研究和病例报告表明瘦素在免疫功能中具有多种作用。然而，缺乏对健康个体进行全面免疫评估的瘦素临床研究。本研究调查了114名健康的绝经后超重或肥胖女性血清瘦素浓度与细胞免疫和炎症的多种生物标志物之间的关联。通过放射免疫分析法测定瘦素。通过比浊法测定C反应蛋白（CRP）和血清淀粉样蛋白A（SAA）。采用流式细胞术测量自然杀伤（NK）细胞的细胞毒性，并对淋巴细胞亚群进行计数和表型分析。通过流式细胞术细胞分裂跟踪法评估对植物血凝素以及抗CD3抗体的T淋巴细胞增殖情况。使用多元线性回归分析，并在适当情况下对混杂因素进行调整和对数转换。血清瘦素浓度与血清CRP、SAA和白细胞介素6（IL6）呈正相关（分别为P<0.0001、P=0.01和P=0.04），在体重指数（BMI）<30 kg/m²的女性中相关性更强。在对测量的身体成分进行调整后，这种关联减弱，但对CRP和SAA仍具有显著性。未观察到瘦素与NK细胞毒性、淋巴细胞亚群或T淋巴细胞增殖之间存在统计学显著关联。本研究填补了关于健康个体中瘦素浓度与免疫功能关系的重要知识空白。研究结果支持血清瘦素与炎症蛋白CRP和SAA之间的关联，这似乎仅部分由脂肪组织介导。我们的研究不支持超重或肥胖但其他方面健康的绝经后女性中瘦素与其他免疫参数之间的联系，可能是因为这种影响仅在瘦素浓度较低或缺乏时才存在。
