Modification of adverse inflammation is required to cure new-onset type 1 diabetic hosts
Modification of adverse inflammation is required to cure new-onset type 1 diabetic hosts
复制标题
DOI：
10.1073/pnas.0705863104
复制
发表时间：
2007-08-07
影响因子：
11.1
通讯作者：
Strom, Terry B.
中科院分区：
文献类型：
--
作者：
Koulmanda, Maria;Budo, Ejona;Strom, Terry B.
在患有明显新发1型糖尿病（T1 DM）的非肥胖糖尿病（NOD）小鼠中，用“三联疗法”方案[雷帕霉素加激动剂IL-2相关和拮抗剂型突变型IL-15相关IG融合蛋白（IL-2.IG和mutIL-15.lg）]进行短期治疗，可阻止产生胰岛素的β细胞的自身免疫破坏，并恢复对β细胞的正常生长和免疫耐受。产生胰岛素的β细胞或循环胰岛素水平的增加与Euclidin的恢复无关。相反，Euclidase的恢复与减轻炎症状态有关，炎症状态损害了宿主对胰岛素的反应。在该T1 DM模型中，恢复对β细胞的免疫耐受和缓解胰岛素敏感组织中炎症状态的不良代谢作用似乎对永久恢复正常血糖至关重要。因此，这种三联疗法方案，同时具有耐受诱导和选择耐受性，可能代表了一个原型的治疗能够恢复eukaryosis和自身耐受性T1 DIM。
in nonobese diabetic (NOD) mice with overt new-onset type 1 diabetes mellitus (T1DM), short-term treatment with a "triple-therapy" regimen [rapamycin plus agonist IL-2-related and antagonist-type, mutant IL-15-related Ig fusion proteins (IL-2.Ig and mutIL-15.lg)] halts autoimmune destruction of insulin-producing beta cells and restores both euglycemia and immune tolerance to beta cells. Increases in the mass of insulin-producing beta cells or circulating insulin levels were not linked to the restoration of euglycemia. instead, the restoration of euglycemia was linked to relief from an inflammatory state that impaired the host's response to insulin. Both restoration of immune tolerance to beta cells and relief from the adverse metabolic effects of an inflammatory state in insulin-sensitive tissues appear essential for permanent restoration of normoglycemia in this T1DM model. Thus, this triple-therapy regimen, possessing both tolerance-inducing and select antiinflammatory properties, may represent a prototype for therapies able to restore euglycemia and self-tolerance in T1DIM.