Influence of metabolic and genetic factors on tumour necrosis factor-alpha and lymphotoxin-alpha production in insulin-dependent diabetes mellitus.
Influence of metabolic and genetic factors on tumour necrosis factor-alpha and lymphotoxin-alpha production in insulin-dependent diabetes mellitus.
复制标题
代谢和遗传因素对胰岛素依赖型糖尿病肿瘤坏死因子-α 和淋巴毒素-α 产生的影响。
作者：
J. Feugeas;H. Caillens;J. Poirier;D. Charron;A. Marcelli;J. Wautier
肿瘤坏死因子(TNF)在自身免疫和胰岛素依赖型糖尿病(IDDM)中的潜在作用，使我们根据肿瘤坏死因子的基因多态性，在体外检测了IDDM患者的肿瘤坏死因子-α和淋巴毒素-α(LT-α，TNF-β)的产生。糖尿病患者外周血单个核细胞产生的LT-α(m=0.30+/-0.2ng.10(-6)细胞)低于对照组(m=0.68+/-0.3ng.10(-6)细胞，p<0.05)，发病年龄早与LT-α产生低相关(r=0.80，p=0.0006)。HbA1c+Gt；或=8%患者的肿瘤坏死因子-α产生水平高于HbA1c+lt；8%患者(m=1.31+/-0.33ng.10(-6)细胞，p<；0.05)。对LTA基因附近的微卫星TNFa区域的研究表明，在人类白细胞抗原-(DR3)受试者中，TNFa1等位基因的存在与IDDM的风险增加有关。TNFa1阳性的受试者(患者和对照组)的LT-α产生也比其他受试者低。这些结果表明，低LT-α的产生是IDDM的另一个危险因素，患者血糖控制不良与PBMC中TNF-α的产生增加有关，从而导致IDDM患者的TNF-α和LT-α的产生失衡。
The potential role of tumour necrosis factors (TNFs) in autoimmunity and insulin-dependent diabetes mellitus (IDDM) led us to determine in vitro TNF-alpha and lymphotoxin-alpha (LT-alpha, TNF-beta) production in IDDM patients according to TNF polymorphism. LT-alpha production of peripheral blood mononuclear cells (PBMC) was lower in diabetic subjects (m = 0.30 +/- 0.2 ng.10(-6) cells) than controls (m = 0.68 +/- 0.3 ng.10(-6) cells, p < 0.05), and early age-at-onset was correlated with low LT-alpha production (rs = 0.8, p = 0.0006). TNF-alpha production was the same in patients and controls, but patients with HbA1c > or = 8% had a higher TNF-alpha production (m = 3.05 +/- 1.2 ng.10(-6) cells) than those with HbA1c < 8% (m = 1.31 +/- 0.33 ng.10(-6) cells, p < 0.05). A study of the microsatellite TNFa region close to the LTA gene showed that the presence of the TNFa1 allele in HLA-(DR3) subjects was associated with increased risk of IDDM. TNFa1-positive subjects (both patients and controls) also had lower LT-alpha production than other subjects. These results indicate that low LT-alpha production is an additional risk factor for IDDM and that poor glycaemic control in patients is associated with enhanced PBMC TNF-alpha production which causes an imbalance between TNF-alpha and LT-alpha production in IDDM patient.