Rothe H, Burkart V, Faust A, Kolb H
Diabetes Research Institute, Heinrich-Heine University, Düsseldorf, Germany.
Diabetologia. 1996 Jan;39(1):119-22. doi: 10.1007/BF00400422.
A single dose of cyclophosphamide (250 mg/kg) is known to synchronize and accelerate development of diabetes in non-obese diabetic mice. We have reported previously that cyclophosphamide treatment of 10-week-old female non-obese diabetic mice induces a shift from T-helper type 2 to T-helper type 1 activity in islet lesions. We now show that this shift in regulatory T-cell function is preceded by the expression of interleukin-12 in the islets as well as in the spleen. In the spleen macrophages were identified as the interleukin-12 expressing cell type. At the same time there was little induction of tumour necrosis factor alpha gene expression by macrophages. Since interleukin-12 is well known to drive T-helper cell type 1 responses we assume that interleukin-12 released by macrophages mediates the accelerating effect of cyclophosphamide on islet inflammation in non-obese diabetic mice. mRNA expression of the p40 chain of interleukin-12 in response to cyclophosphamide was not seen in macrophages of Balb/c mice and thus represents an immune abnormality of non-obese diabetic mice favouring T-helper type 1 reactions.
已知单剂量环磷酰胺（250毫克/千克）可使非肥胖型糖尿病小鼠的糖尿病发展同步并加速。我们之前报道过，用环磷酰胺处理10周龄雌性非肥胖型糖尿病小鼠会导致胰岛病变中从辅助性T细胞2型活性向辅助性T细胞1型活性转变。我们现在表明，在调节性T细胞功能发生这种转变之前，胰岛以及脾脏中会有白细胞介素-12的表达。在脾脏中，巨噬细胞被确定为表达白细胞介素-12的细胞类型。与此同时，巨噬细胞对肿瘤坏死因子α基因表达的诱导作用很小。由于众所周知白细胞介素-12可驱动辅助性T细胞1型反应，我们推测巨噬细胞释放的白细胞介素-12介导了环磷酰胺对非肥胖型糖尿病小鼠胰岛炎症的加速作用。在Balb/c小鼠的巨噬细胞中未观察到环磷酰胺刺激下白细胞介素-12 p40链的mRNA表达，因此这代表了非肥胖型糖尿病小鼠有利于辅助性T细胞1型反应的免疫异常。
