Prevention of a Th1 disease by a Th1 cytokine: IL-12 and diabetes in NOD mice.
The effects of interleukin-12 on autoimmune diabetes in nonobese diabetic mice was examined. IL-12 was given, intraperitoneally, to NOD females in two different treatment protocols: three times a week, for 2 weeks beginning at 9 weeks of age and a single weekly injection, for 15 weeks, beginning at 9 weeks of age. A significant decrease in diabetes incidence was observed with multidose/short-term IL-12 treatment. Age of disease onset, however, was unchanged. Weekly administration of IL-12 was more effective in preventing onset of diabetes. Only 20% of female NOD mice become diabetic by 30 weeks of age, with a later age of onset. In spite of the decrease in diabetes incidence, no differences were seen in islet histology with treated mice compared to controls. Furthermore, IL-12 treatment of recipient mice did not prevent induction of diabetes using spleen cells from diabetic mice in adoptive transfer experiments. These observations are in contrast to reported data in which treatment of NOD mice with daily doses of IL-12 exacerbated disease incidence and hastened diabetes onset.
O'Hara
R M
RM
Genetics Institute, Laboratory of Molecular Immunology, Cambridge, Massachusetts 02140, USA.
Henderson
S L
SL
Nagelin
A
A
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma