Endogenous interleukin-12 only plays a key pathogenetic role in non-obese diabetic mouse diabetes during the very early stages of the disease.
A rat monoclonal antibody (mAb) that neutralizes mouse interleukin-12 (IL-12) was administered to female non-obese diabetic (NOD) mice of different ages to dismantle the role of endogenous IL-12 in murine autoimmune diabetogenesis. This mAb was effective in preventing clinical, but not histological signs of spontaneous diabetes when treatment was started early in life at the age of 4 weeks and consecutively continued for 10 weeks. Delaying commencement of anti-IL-12 mAb prophylaxis until the age of 18 weeks, when NOD mice suffer from advanced insulitis, was ineffective. Anti-IL-12 mAb did not influence the course of the accelerated model of diabetes induced by cyclophosphamide. These data prove that the pathogenetic role of endogenous IL-12 in NOD mouse diabetes is restricted to the very early diabetogenic events presumably occurring prior to insulitis development.
Nicoletti
F
F
Institute of Microbiology, University of Milan, Italy.
Di Marco
R
R
Zaccone
P
P
Magro
G
G
Di Mauro
M
M
Grasso
S
S
Meroni
P L
PL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D018664:Interleukin-12 / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D051381:Rats
D000911:Antibodies, Monoclonal; D018664:Interleukin-12