Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, Massachusetts 02111, USA.
J Endocrinol. 2010 Aug;206(2):217-24. doi: 10.1677/JOE-10-0057. Epub 2010 May 18.
Inflammation plays a central role in the development and progression of coronary heart disease (CHD). The sex hormones estrogen and testosterone have been shown to modify the inflammatory response by influencing cytokine expression in human macrophages obtained from younger individuals. The effect of these hormones on the expression of proinflammatory markers in macrophages obtained from a CHD age-relevant population has not been studied. Human monocyte-derived macrophages (HMDMs) were obtained from healthy normolipidemic men and postmenopausal women (age 50-70 years), and cultured in autologous serum along with both physiological and supraphysiological concentrations of estrogen or testosterone. HMDMs were stimulated with oxidized low-density lipoproteins, and the expression of the cytokines tumor necrosis factor alpha (TNF-alpha or TNF), interleukin (IL)6, and IL-1 beta (IL1B) and of the acute-phase protein C-reactive protein (CRP) was measured. Both physiological and supraphysiological concentrations of testosterone reduced the expression and secretion of TNF-alpha and reduced the expression of IL-1 beta, but did not affect the expression of IL6 or CRP. Estrogen did not modify the expression of TNF-alpha, IL6, and IL-1 beta. Estrogen caused a variable response in CRP expression that was positively associated with the plasma small dense LDL-cholesterol concentration of the donors. There were no gender differences in any of the observed effects. Our results indicate that testosterone may exert anti-inflammatory effects by reducing macrophage TNF-alpha expression, while the effects of estrogen on macrophage CRP expression may depend upon the extracellular lipid environment.
炎症在冠心病（CHD）的发展和进展中起着核心作用。雌激素和睾丸激素等性激素通过影响从年轻人获得的人巨噬细胞中的细胞因子表达，从而改变炎症反应。这些激素对从 CHD 相关年龄人群获得的巨噬细胞中促炎标志物表达的影响尚未研究。从健康的正常血脂男性和绝经后女性（年龄 50-70 岁）中获得人单核细胞衍生的巨噬细胞（HMDM），并在自体血清中与生理和超生理浓度的雌激素或睾丸激素一起培养。用氧化的低密度脂蛋白刺激 HMDM，测量细胞因子肿瘤坏死因子-α（TNF-α或 TNF）、白细胞介素（IL）6 和 IL-1β（IL1B）以及急性期蛋白 C 反应蛋白（CRP）的表达。生理和超生理浓度的睾丸酮均降低 TNF-α的表达和分泌，并降低 IL-1β的表达，但不影响 IL6 或 CRP 的表达。雌激素未修饰 TNF-α、IL6 和 IL-1β的表达。雌激素引起 CRP 表达的可变反应，与供体的血浆小而密 LDL-胆固醇浓度呈正相关。在观察到的任何影响中都没有性别差异。我们的结果表明，睾丸酮可能通过降低巨噬细胞 TNF-α的表达发挥抗炎作用，而雌激素对巨噬细胞 CRP 表达的影响可能取决于细胞外脂质环境。
