Smith Alexia G, Sheridan Patricia A, Harp Joyce B, Beck Melinda A
Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA.
J Nutr. 2007 May;137(5):1236-43. doi: 10.1093/jn/137.5.1236.
Obesity is associated with an impaired immune response, an increased susceptibility to bacterial infection, and a chronic increase in proinflammatory cytokines such as IL-6 and TNFalpha. However, few studies have examined the effect of obesity on the immune response to viral infections. Because infection with influenza is a leading cause of morbidity and mortality worldwide, we investigated the effect of obesity on early immune responses to influenza virus exposure. Diet-induced obese and lean control C57BL/6 mice were infected with influenza A/PR8/34, and lung pathology and immune responses were examined at d 0 (uninfected), 3, and 6, postinfection. Following infection, diet-induced obese mice had a significantly higher mortality rate than the lean controls and elevated lung pathology. Antiviral and proinflammatory cytokine mRNA production in the lungs of the infected mice was markedly different between obese and lean mice. IFNalpha and beta were only minimally expressed in the infected lungs of obese mice and there was a notable delay in expression of the proinflammatory cytokines IL-6 and TNFalpha. Additionally, obese mice had a substantial reduction in NK cell cytotoxicity. These data indicate that obesity inhibits the ability of the immune system to appropriately respond to influenza infection and suggests that obesity may lead to increased morbidity and mortality from viral infections.
肥胖与免疫反应受损、细菌感染易感性增加以及促炎细胞因子（如白细胞介素-6和肿瘤坏死因子α）的持续升高有关。然而，很少有研究探讨肥胖对病毒感染免疫反应的影响。由于流感感染是全球发病和死亡的主要原因，我们研究了肥胖对流感病毒暴露早期免疫反应的影响。用饮食诱导肥胖和瘦对照C57BL/6小鼠感染甲型流感病毒A/PR8/34，并在感染后第0天（未感染）、3天和6天检查肺部病理和免疫反应。感染后，饮食诱导肥胖小鼠的死亡率显著高于瘦对照小鼠，肺部病理情况也有所加重。感染小鼠肺部抗病毒和促炎细胞因子mRNA的产生在肥胖小鼠和瘦小鼠之间存在显著差异。干扰素α和β在肥胖小鼠感染的肺部中仅微量表达，促炎细胞因子白细胞介素-6和肿瘤坏死因子α的表达明显延迟。此外，肥胖小鼠的自然杀伤细胞细胞毒性大幅降低。这些数据表明，肥胖会抑制免疫系统对流感感染做出适当反应的能力，并提示肥胖可能导致病毒感染的发病率和死亡率增加。
