Satoh J, Seino H, Abo T, Tanaka S, Shintani S, Ohta S, Tamura K, Sawai T, Nobunaga T, Oteki T
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
J Clin Invest. 1989 Oct;84(4):1345-8. doi: 10.1172/JCI114304.
We previously reported that administration of a streptococcal preparation (OK-432) inhibited insulitis and development of autoimmune diabetes in nonobese diabetic (NOD) mice and BB rats as animals models of insulin-dependent diabetes mellitus. In this study, we screened various cytokines that could be induced by OK-432 in vivo, for their preventive effect against diabetes in NOD mice. Among recombinant mouse IFN gamma, human IL1 alpha, human IL2, mouse granulocyte-macrophage colony-stimulating factor and human TNF alpha, only human TNF alpha suppressed insulitis and significantly (P less than 0.001) inhibited development of diabetes. NOD mice were the lowest producers of the mRNA of TNF and serum TNF on stimulation with OK-432 or with IFN gamma plus LPS, compared with C57BL/6, C3H/He, and Balb/c mice. The results imply a role for low productivity of TNF in the pathogenesis of autoimmune diabetes in NOD mice.
我们之前报道过，给予链球菌制剂（OK-432）可抑制作为胰岛素依赖型糖尿病动物模型的非肥胖糖尿病（NOD）小鼠和BB大鼠的胰岛炎及自身免疫性糖尿病的发展。在本研究中，我们筛选了OK-432在体内可诱导产生的各种细胞因子，以观察它们对NOD小鼠糖尿病的预防作用。在重组小鼠干扰素γ、人白细胞介素1α、人白细胞介素2、小鼠粒细胞-巨噬细胞集落刺激因子和人肿瘤坏死因子α中，只有人肿瘤坏死因子α抑制了胰岛炎，并显著（P<0.001）抑制了糖尿病的发展。与C57BL/6、C3H/He和Balb/c小鼠相比，NOD小鼠在用OK-432或干扰素γ加脂多糖刺激时，肿瘤坏死因子mRNA和血清肿瘤坏死因子的产生量最低。这些结果表明肿瘤坏死因子低产生率在NOD小鼠自身免疫性糖尿病发病机制中起作用。
