Inhibition of diabetes in NOD mice by human pregnancy factor.
Clinical symptoms of Th1 mediated autoimmune diseases regress in many patients during pregnancy. A prominent feature of pregnancy is the presence of human chorionic gonadotrophin hormone (hCG) in blood and urine. In this report we tested the effect of clinical grade hCG (c-hCG) on the development of diabetes, a Th1 mediated autoimmune disease, in nonobese diabetic (NOD) mice. We show that treatment of NOD mice with c-hCG before the onset of clinical symptoms lowered the increased blood glucose levels, reversed the established inflammatory infiltrate of pancreatic tissue, and profoundly inhibited the development of diabetes for prolonged time. c-hCG also induced profound inhibition of the functional activity (i.e. production of IFN-gamma) of Th1 cells. Transfer of spleen cells from c-hCG-treated NOD mice into immunocompromised NOD.SCID mice inhibited the development of diabetes in these otherwise nontreated mice. This shows that the treatment of the donor NOD mice induced persistent changes in the immune system. The antidiabetic activity of c-hCG was not caused by heterodimeric hCG or its subunits. Instead, this antidiabetic activity resided in a fraction of c-hCG preparation that contains a 400-2000 Dalton natural (immuno) modulatory pregnancy factor (NMPF).
Khan
N A
NA
Department of Immunology, Erasmus University and University Hospital Rotterdam, P.O. Box 1738, Rotterdam, The Netherlands.
Khan
A
A
Savelkoul
H F
HF
Benner
R
R
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010179:Pancreas / Q000166:cytology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*
D001786:Blood Glucose; D006063:Chorionic Gonadotropin; D007371:Interferon-gamma