Fontana Luigi, Eagon J Christopher, Colonna Marco, Klein Samuel
Division of Geriatrics and Nutritional Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Rejuvenation Res. 2007 Mar;10(1):41-6. doi: 10.1089/rej.2006.0504.
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 [IFNgamma]) production, which is an important component of the immune response to infectious pathogens.
Lipopolysaccharide (LPS)and phorbol 12-myristate 13-acetate plus ionomycin (PMA + I)-stimulated PBMC MCP-1 and IFNgamma 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)).
At baseline, LPS-stimulated MCP-1 production and PMAI-stimulated IFNgamma 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 IFNgamma production in obese subjects to normal.
Agonist-stimulated production of IFNgamma 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 IFNgamma. 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.
肥胖与感染的患病率增加及严重程度加重相关。导致感染风险增加的机制尚不清楚。我们评估了过度肥胖及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 [IFNγ]）产生的影响，而这些是对感染性病原体免疫反应的重要组成部分。
在6名极度肥胖受试者（体重指数[BMI]=62.4±8.6kg/m²）接受胃旁路手术前及术后1年，以及6名年龄匹配的瘦人受试者（BMI=22.7±1.4kg/m²）中，测定脂多糖（LPS）及佛波醇12-肉豆蔻酸酯13-乙酸酯加离子霉素（PMA+I）刺激的PBMC的MCP-1和IFNγ产生情况。
在基线时，肥胖受试者中LPS刺激的PBMC的MCP-1产生及PMA+I刺激的IFNγ产生分别比瘦人受试者低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年体重减轻了30.3%±10.6%（p<0.001）。体重减轻使肥胖受试者中LPS刺激的MCP-1产生及PMA+I刺激的IFNγ产生完全恢复正常。
在极度肥胖受试者中，激动剂刺激的IFNγ和MCP-1产生明显受到抑制。体重减轻使受刺激PBMC产生MCP-1和IFNγ的能力完全恢复正常。这些发现对于理解与肥胖相关的感染风险增加可能具有重要意义，并证明了体重减轻对免疫功能具有独特的有益作用。
