Mærkedahl Rasmus Baadsgaard, Frøkiær Hanne, Stenbæk Marie Grøntved, Nielsen Camilla Betak, Lind Mads V, Lundtoft Christian, Bohr Marietta Boje, Ibrügger Sabine, Metzdorff Stine Broeng, Vestergaard Henrik, Pedersen Oluf, Lauritzen Lotte
1 Department of Nutrition, Exercise, and Sports, University of Copenhagen , Frederiksberg C, Denmark .
2 Department of Veterinary and Animal Sciences, University of Copenhagen , Frederiksberg C, Denmark .
Metab Syndr Relat Disord. 2018 Feb;16(1):29-39. doi: 10.1089/met.2017.0121. Epub 2018 Jan 10.
Low-grade systemic inflammation (LGSI) is often characterized by elevated levels of interleukin (IL)6, tumor necrosis factor (TNF)α, and C-reactive protein (CRP). Other serum proteins, ex vivo-stimulated cytokine production, and leukocyte count have, however, also been suggested LGSI-markers, but their associations with the metabolic syndrome (MS) are less clear. We aimed to evaluate mutual relationships between in vivo and ex vivo inflammatory markers and their association with MS and its subcomponents.
A cross-sectional study of 118 overweight adults with one or several features of MS. Inflammatory markers included fasting serum levels of IL6, TNFα, CRP, and pentraxin-3 (PTX3), IL1-receptors, leukocytes, and whole-blood ex vivo-produced IL1β, IL6, TNFα, and IL8 after lipopolysaccharide stimulation.
All classical serum LGSI-markers correlated with each other, and IL6 and CRP were also correlated with leukocyte count. Ex vivo-produced cytokines were intercorrelated and correlated with leukocyte count, but did not correlate with the serum immune markers. MS score, body mass index, and glycated hemoglobin (HbA1c) were associated with 8%-16% higher inflammatory score per standard deviation increment (P = 0.030, 0.001, and 0.034, respectively), primarily driven by higher serum IL6. Serum PTX3 was only significantly associated with high-density lipoprotein cholesterol (1.19[1.04; 1.37], P = 0.013). HbA1c was inversely associated with surface expression of IL1R1 on monocytes and IL1R2 on granulocytes (P < 0.01) and with a 3%-9% lower ex vivo production of cytokines when adjusting for leukocyte count, as were plasma triacylglycerol (9%-10% lower IL1β and IL6). Leukocyte count was most consistently associated with MS and its subcomponents, although not with HbA1.
The classical fasting serum markers of LGSI and leukocyte counts associated best with measures of MS-associated LGSI, whereas ex vivo cytokine production was only associated with prevailing glycemia and dyslipidemia. Taken together, this indicates that the relationship between in vivo and ex vivo inflammatory markers is complex and may depend on the MS phenotype.
低度全身炎症（LGSI）通常表现为白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α和C反应蛋白（CRP）水平升高。然而，其他血清蛋白、体外刺激的细胞因子产生以及白细胞计数也被认为是LGSI的标志物，但其与代谢综合征（MS）的关联尚不清楚。我们旨在评估体内和体外炎症标志物之间的相互关系及其与MS及其亚组分的关联。
对118名有一项或多项MS特征的超重成年人进行横断面研究。炎症标志物包括空腹血清中IL-6、TNF-α、CRP和五聚素-3（PTX3）水平、IL-1受体、白细胞，以及脂多糖刺激后全血体外产生的IL-1β、IL-6、TNF-α和IL-8。
所有经典的血清LGSI标志物之间均相互关联，IL-6和CRP也与白细胞计数相关。体外产生的细胞因子相互关联且与白细胞计数相关，但与血清免疫标志物无关。MS评分、体重指数和糖化血红蛋白（HbA1c）每增加一个标准差，炎症评分分别升高8%-16%（P分别为0.030、0.001和0.034），主要由血清IL-6升高驱动。血清PTX3仅与高密度脂蛋白胆固醇显著相关（1.19[1.04；1.37]，P = 0.013）。校正白细胞计数后，HbA1c与单核细胞表面IL-1R1和粒细胞表面IL-1R2的表达呈负相关（P < 0.01），且与体外细胞因子产生降低3%-9%相关，血浆甘油三酯也如此（IL-1β和IL-6降低9%-10%）。白细胞计数与MS及其亚组分的关联最为一致，尽管与HbA1无关。
LGSI的经典空腹血清标志物和白细胞计数与MS相关LGSI的指标关联最佳，而体外细胞因子产生仅与血糖和血脂异常相关。综上所述，这表明体内和体外炎症标志物之间的关系很复杂，可能取决于MS的表型。
