H. Rothe et al., INTERLEUKIN-12 GENE-EXPRESSION IS ASSOCIATED WITH RAPID DEVELOPMENT OF DIABETES-MELLITUS IN NONOBESE DIABETIC MICE, Diabetologia, 39(1), 1996, pp. 119-122
Citations number
10
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
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-ol
d 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 sh
ift in regulatory T-cell function is preceded by the expression of int
erleukin-12 in the islets as well as in the spleen. In the spleen macr
ophages were identified as the interleukin-12 expressing cell type. At
the same time there was little induction of tumour necrosis factor al
pha 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 cyclophos
phamide on islet inflammation in non-obese diabetic mice. mRNA express
ion of the p40 chain of interleukin-12 in response to cyclophosphamide
was not seen in macrophages of Balb/c mice and thus represents an imm
une abnormality of non-obese diabetic mice favouring T-helper type 1 r
eactions.