O'Rourke R W, Kay T, Lyle E A, Traxler S A, Deveney C W, Jobe B A, Roberts C T, Marks D, Rosenbaum J T
Department of Surgery, Oregon Health and Science University, Portland, OR 97239, USA.
Clin Exp Immunol. 2006 Oct;146(1):39-46. doi: 10.1111/j.1365-2249.2006.03186.x.
Obesity is characterized by alterations in immune and inflammatory function. In order to evaluate the potential role of cytokine expression by peripheral blood mononuclear cells (PBMC) in obesity-associated inflammation, we studied serum protein levels and mRNA levels in PBMC of interleukin (IL)-6, IL-1beta, tumour necrosis factor (TNF)-alpha and IL-1Ra in nine lean and 10 obese subjects. Serum IL-1beta was undetectable, IL-1Ra serum levels were elevated, serum levels of TNF-alpha were decreased and serum levels of IL-6 were similar in obese subjects compared to lean subjects, while transcript levels of IL-6, IL-1beta and TNF-alpha, but not IL-1Ra, were decreased in PBMC from obese subjects. PBMC from obese subjects did, however, up-regulate cytokine expression in response to leptin. Thus, obesity-associated changes in IL-1Ra serum levels and IL-6 mRNA levels were not correlated with changes in cognate mRNA and serum levels, respectively, while TNF-alpha serum levels and PBMC mRNA levels were both decreased in obese patients. While immune alterations in obesity are manifest in peripheral blood lymphocytes, the general lack of correlation between altered serum levels and altered PBMC gene expression suggests that PBMC may not be the source of aberrant serum cytokine levels in obesity.
肥胖的特征是免疫和炎症功能发生改变。为了评估外周血单核细胞(PBMC)表达的细胞因子在肥胖相关炎症中的潜在作用,我们研究了9名瘦人和10名肥胖受试者的血清蛋白水平以及PBMC中白细胞介素(IL)-6、IL-1β、肿瘤坏死因子(TNF)-α和IL-1Ra的mRNA水平。与瘦人相比,肥胖受试者血清中IL-1β检测不到,IL-1Ra血清水平升高,TNF-α血清水平降低,IL-6血清水平相似,而肥胖受试者PBMC中IL-6、IL-1β和TNF-α的转录水平降低,但IL-1Ra的转录水平未降低。然而,肥胖受试者的PBMC确实会因瘦素而上调细胞因子表达。因此,肥胖相关的IL-1Ra血清水平和IL-6 mRNA水平变化分别与相应的mRNA和血清水平变化无关,而肥胖患者的TNF-α血清水平和PBMC mRNA水平均降低。虽然肥胖中的免疫改变在外周血淋巴细胞中表现明显,但血清水平改变与PBMC基因表达改变之间普遍缺乏相关性,这表明PBMC可能不是肥胖中异常血清细胞因子水平的来源。