RECOMBINANT HUMAN IL-1O PREVENTS THE ONSET OF DIABETES IN THE NONOBESE DIABETIC MOUSE
RECOMBINANT HUMAN IL-1O PREVENTS THE ONSET OF DIABETES IN THE NONOBESE DIABETIC MOUSE
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DOI：
10.1006/clin.1994.1068
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发表时间：
1994-05-01
期刊：
影响因子：
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通讯作者：
MONAHAN, M
中科院分区：
文献类型：
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作者：
PENNLINE, KJ;ROQUEGAFFNEY, E;MONAHAN, M
在非肥胖糖尿病（NOD）小鼠中评估了IL-10在自身免疫性糖尿病发病机制中的作用。在这些研究中，确定了IL-10对糖尿病的三个参数的影响：高血糖的发展、胰岛素的发展和β细胞产生胰岛素。最初的实验研究了抗细胞因子抗体对疾病发展的影响。上述结果表明，单克隆抗ifn - γ抗体可显著降低雌性NOD小鼠高血糖的发生率，而抗il -4、IL-5和IL-10则无效。在随后的研究中，每日皮下给予IL-10（一种已知的TH1 T细胞产生ifn - γ的有效抑制剂）给9周和10周大的nod可以延缓疾病的发生并显著降低糖尿病的发病率。在胰腺组织上进行的组织病理学研究表明，用IL-10治疗可以减轻胰岛素炎的严重程度，阻止胰岛细胞的细胞浸润，并促进β细胞正常的胰岛素分泌。综上所述，这些结果表明IL-10抑制与糖尿病相关的自身免疫性发病机制的诱导和进展，并提示该细胞因子在这种自身免疫性疾病中的潜在治疗作用。(C) 1994学术出版社，Inc.
The role of IL-10 in the pathogenesis of autoimmune diabetes mellitus was assessed in the nonobese diabetic (NOD) mouse. In these studies the effect of IL-10 was determined on three parameters of diabetes: The development of hyperglycemia, the development of insulitis, and the production of insulin by beta cells. Initial experiments investigated the effect of anticytokine antibodies on the development of disease. These results indicated that monoclonal anti-IFN-gamma antibody greatly reduced the incidence of hyperglycemia in female NOD mice, while anti-IL-4, IL-5, and IL-10 were ineffective. In subsequent studies, daily subcutaneous administration of IL-10, a known potent inhibitor of IFN-gamma production by TH1 T cells, to 9 and 10-week-old NODs was shown to delay the onset of disease and significantly reduce the incidence of diabetes. Histopathology performed on pancreatic tissue demonstrated that treatment with IL-10 reduced the severity of insulitis, prevented cellular infiltration of islet cells, and promoted normal insulin production by beta cells. Taken together these results indicate IL-10 suppresses the induction and progression of autoimmune pathogenesis associated with diabetes mellitus and suggest a potential therapeutic role for this cytokine in this autoimmune disease. (C) 1994 Academic Press, Inc.