Impaired mononuclear cell immune function in extreme obesity is corrected by weight loss
Impaired mononuclear cell immune function in extreme obesity is corrected by weight loss
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DOI：
10.1089/rej.2006.0504
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发表时间：
2007-03-01
影响因子：
2.6
通讯作者：
Klein, Samuel
中科院分区：
文献类型：
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作者：
Fontana, Luigi;Eagon, J. Christopher;Klein, Samuel
背景：肥胖与感染的患病率和严重程度增加有关。导致感染风险增加的机制尚不清楚。我们评估了过度肥胖和体重减轻对外周血单核细胞（PBMC）趋化因子（巨噬细胞趋化蛋白-1 [MCP-1]）和细胞因子（干扰素-γ [IFN-γ]）产生的影响，这是对感染性病原体的免疫应答的重要组成部分。研究方法：在6名极度肥胖的受试者中测定脂多糖（LPS）和佛波醇12-肉豆蔻酸酯13-乙酸酯加离子霉素（PMA+I）刺激的PBMC MCP-1和IFN-γ的产生在胃旁路手术前和手术后1年（体重指数[BMI] = 62.4 +/- 8.6 kg/m2）以及6名年龄匹配的瘦型受试者（BMI = 22.7 +/- 1.4 kg/m2）中进行研究。结果如下：在基线时，肥胖受试者中LPS刺激的MCP-1产生和PMA+ I刺激的IFN-γ产生分别比瘦受试者低93.6% +/- 4.9%和88.8% +/- 9.6%（p < 0.03）。肥胖受试者在胃旁路手术后1年体重减轻30.3% ± 10.6%（p < 0.001）。体重减轻完全恢复了肥胖受试者中LPS刺激的MCP-1产生和PMA+ I刺激的IFN-γ产生。结论：在极度肥胖的受试者中，激动剂刺激的IFN-γ和MCP-1的产生明显受到抑制。体重减轻使受刺激的PBMC产生MCP-1和IFN-γ的能力完全正常化。这些发现可能对理解与肥胖相关的感染风险增加具有重要意义，并证明减肥对免疫功能具有独特的有益作用。
Background: Obesity is associated with an increased prevalence, and severity of infections. The mechanism(s) responsible for the increased risk of infections is unclear. We evaluated the effects of excessive adiposity and weight loss on peripheral blood mononuclear cell (PBMC) chemokine (macrophage chemoattractant protein-1 [MCP-1) and cytokine (interferon-gamma [IFN-gamma]) production, which is an important component of the immune response to infectious pathogens. Methods: Lipopolysaccharide (LPS)- and phorbol 12-myristate 13-acetate plus ionomycin (PMA+I)-stimulated PBMC MCP-1 and IFN-gamma production were determined in six extremely obese subjects (body mass index [BMI] = 62.4 +/- 8.6 kg/m(2)) before and 1 year after gastric bypass surgery and in six age-matched lean subjects (BMI = 22.7 +/- 1.4 kg/m(2)). Results: At baseline, LPS-stimulated MCP-1 production and PMA+I-stimulated IFN-gamma production by PBMCs were 93.6% +/- 4.9% and 88.8% +/- 9.6% lower, respectively, in obese than in lean subjects (p < 0.03). Obese subjects lost 30.3% +/- 10.6% of their body weight at 1 year after gastric bypass surgery (p < 0.001). Weight loss completely restored LPS-stimulated MCP-1 production and PMA+I-stimulated IFN-gamma production in obese subjects to normal. Conclusions: Agonist-stimulated production of IFN-gamma and MCP-1 are markedly suppressed in subjects with extreme obesity. Weight loss completely normalizes the ability of stimulated PBMCs to produce MCP-1 and IFN-gamma. These findings could have important implications in understanding the increased risk of infections associated with obesity, and demonstrate a unique beneficial effect of weight loss on immune function.