| First Author | Rothe H | Year | 1996 |
| Journal | Diabetologia | Volume | 39 |
| Issue | 1 | Pages | 119-22 |
| PubMed ID | 8720612 | Mgi Jnum | J:31148 |
| Mgi Id | MGI:78632 | Doi | 10.1007/BF00400422 |
| Citation | Rothe H, et al. (1996) Interleukin-12 gene expression is associated with rapid development of diabetes mellitus in non-obese diabetic mice. Diabetologia 39(1):119-22 |
| abstractText | 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. |
