Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612, United States.
Cytokine. 2013 Jan;61(1):71-7. doi: 10.1016/j.cyto.2012.08.027. Epub 2012 Sep 23.
Obesity is associated with elevated levels of IL-6. High IL-6 is prognostic of mortality in sepsis, while controversial data link obesity to sepsis outcome. We used Lean and diet-induced obese (DIO) WT and IL-6 KO mice to investigate the interaction between obesity and IL-6 in endotoxemia. Circulating levels of IL-6 were significantly higher in WT DIO versus WT Lean mice receiving LPS (2.5 μg/mouse, ip). Obesity lead to greater weight loss in response to LPS, with IL-6 deficiency being partially protective. Plasma TNFα, IFNγ, Galectin-3 and leptin were significantly elevated in response to LPS and were each differentially affected by obesity and/or IL-6 deficiency. Plasma Galectin-1 and adiponectin were significantly suppressed by LPS, with obesity and IL-6 deficiency modulating the response. However, LPS comparably increased IL-10 levels in each group. Leukopenia with relative neutrophilia and thrombocytopenia developed in each group after injection of LPS, with obesity and genotype affecting the kinetics, but not the magnitude, of the response. Hepatic induction of the acute-phase protein SAA by LPS was not affected by obesity or IL-6 deficiency, although baseline levels were highest in WT DIO mice. Injection of LPS significantly increased hepatic mRNA expression of PAI-1 in Lean WT and Lean KO mice, while it suppressed the high baseline levels observed in the liver of DIO WT and DIO KO mice. Thus, both IL-6 and obesity modulate the response to endotoxemia, suggesting a complex interaction that needs to be considered when evaluating the effect of obesity on the outcome of septic patients.
肥胖与白细胞介素 6（IL-6）水平升高有关。高 IL-6 是脓毒症患者死亡率的预后指标，而有争议的数据则将肥胖与脓毒症的结果联系起来。我们使用瘦素（Leptin）和饮食诱导肥胖（DIO）WT 和 IL-6 KO 小鼠来研究肥胖与内毒素血症中 IL-6 之间的相互作用。在接受 LPS（2.5μg/只，腹腔注射）的 WT DIO 与 WT Lean 小鼠中，循环 IL-6 水平显著升高。肥胖导致 LPS 反应时体重下降更大，而 IL-6 缺乏则部分具有保护作用。血浆 TNFα、IFNγ、半乳糖凝集素-3 和瘦素对 LPS 的反应显著升高，并且受到肥胖和/或 IL-6 缺乏的不同影响。血浆半乳糖凝集素-1 和脂联素受到 LPS 的显著抑制，肥胖和 IL-6 缺乏调节了这种反应。然而，LPS 以相似的方式增加了每组的 IL-10 水平。在每组注射 LPS 后，均出现白细胞减少症伴相对中性粒细胞增多和血小板减少症，肥胖和基因型影响反应的动力学，但不影响反应的幅度。LPS 对内毒素血症时肝组织中急性期蛋白 SAA 的诱导不受肥胖或 IL-6 缺乏的影响，尽管在 WT DIO 小鼠中基础水平最高。LPS 注射显著增加了 Lean WT 和 Lean KO 小鼠肝脏中 PAI-1 的 mRNA 表达，而抑制了 DIO WT 和 DIO KO 小鼠肝脏中观察到的高基线水平。因此，IL-6 和肥胖都调节了对内毒素血症的反应，这表明在评估肥胖对脓毒症患者结果的影响时，需要考虑到这种复杂的相互作用。
