Pacifico Lucia, Di Renzo Livia, Anania Caterina, Osborn John F, Ippoliti Flora, Schiavo Elisa, Chiesa Claudio
Department of Pediatrics, La Sapienza University of Rome, Italy.
Eur J Endocrinol. 2006 May;154(5):691-7. doi: 10.1530/eje.1.02138.
Leptin, an adipocyte-secreted hormone, has emerged as a potential candidate for the link between obesity and the proinflammatory state. Specifically, leptin modulates T-helper (Th) cells toward a Th1 phenotype, with the secretion of proinflammatory cytokines. The aim of this study was to evaluate the Th1/Th2 balance in obese children and its relation with hormonal and metabolic features.
In 50 obese children and 20 control children, we measured the CD4-positive Th cells that secrete interferon (IFN)-gamma or interleukin (IL)-2 (taken as an index of Th1 cells), and IL-4 (taken as an index of Th2 cells) as well as serum glucose, insulin, insulin resistance (IR) index (as homeostasis model assessment model (HOMA)), lipid profile, aminotransferases, leptin and ghrelin. Obese children also underwent dual energy X-ray absorptiometry scan measurements, and liver ultrasound scanning.
Geometric mean percentages of IL-2- and IL-4-CD4 secreting cells in obese children were not significantly different from those found in control children. However, the geometric mean percentage of CD4-positive T cells secreting IFN-gamma was significantly higher in the obese than in the control (P < 0.0001, t-test) group. Within the entire group of study children, the percentage of IFN-gamma-positive cells was positively associated with leptin (P = 0.002), insulin (P < 0.00 005), and HOMA-IR values (P < 0.00 005). However, when these associations were restricted to the group of obese subjects, insulin and HOMA-IR values, but not leptin, retained statistical significance. Yet, in the obese group, the percentage of IFN-gamma-positive cells was associated with nonalcoholic steatohepatitis (NASH) (P = 0.001), but not with body mass index-standard deviation score and total body fat mass.
In obese children, a shift to Th1-cytokine profile dominated by the production of IFN-gamma is related to insulin resistance as well as to NASH independently of anthropometric features and other metabolic characteristics. The prevalent Th1 pattern of secreted cytokines may be regarded as a mechanism contributing to inflammation in obesity.
瘦素是一种由脂肪细胞分泌的激素，已成为肥胖与促炎状态之间联系的潜在候选因素。具体而言，瘦素可使辅助性T（Th）细胞向Th1表型转变，并分泌促炎细胞因子。本研究旨在评估肥胖儿童的Th1/Th2平衡及其与激素和代谢特征的关系。
我们对50名肥胖儿童和20名对照儿童进行了检测，测量了分泌干扰素（IFN）-γ或白细胞介素（IL）-2的CD4阳性Th细胞（作为Th1细胞的指标）、IL-4（作为Th2细胞的指标）以及血清葡萄糖、胰岛素、胰岛素抵抗（IR）指数（作为稳态模型评估模型（HOMA））、血脂谱、转氨酶、瘦素和胃饥饿素。肥胖儿童还接受了双能X线吸收法扫描测量和肝脏超声扫描。
肥胖儿童中分泌IL-2和IL-4的CD4细胞的几何平均百分比与对照儿童无显著差异。然而，肥胖儿童中分泌IFN-γ的CD4阳性T细胞的几何平均百分比显著高于对照组（P<0.0001，t检验）。在整个研究儿童组中，IFN-γ阳性细胞的百分比与瘦素（P = 0.002）、胰岛素（P<0.00005）和HOMA-IR值（P<0.00005）呈正相关。然而，当这些关联仅限于肥胖受试者组时，胰岛素和HOMA-IR值（而非瘦素）仍具有统计学意义。此外，在肥胖组中，IFN-γ阳性细胞的百分比与非酒精性脂肪性肝炎（NASH）相关（P = 0.001），但与体重指数标准差评分和全身脂肪量无关。
在肥胖儿童中，以IFN-γ产生为主导的向Th1细胞因子谱的转变与胰岛素抵抗以及NASH相关，且独立于人体测量特征和其他代谢特征。分泌细胞因子的普遍Th1模式可能被视为肥胖中炎症发生的一种机制。
