Immunostimulation by complete Freund's adjuvant, granulocyte macrophage colony-stimulating factor, or interferon-gamma reduces severity of diabetic embryopathy in ICR mice.
BACKGROUND
Increased risk of fetal malformation is a complication occurring in pregnant women with type 1 diabetes. Local (uterine) immune stimulation has been shown to reduce diabetes-induced teratogenesis in mice. Limited information is available regarding the ability of diverse methods of maternal immune stimulation to cause this effect or regarding timing requirements of the immune stimulation.


METHODS
Diabetes was induced in pregnant ICR mice by streptozocin (STZ) injection. Three different techniques of maternal immune stimulation, complete Freund's adjuvant (CFA), granulocyte-macrophage colony-stimulating factor (GM-CSF), or interferon-gamma (IFN-gamma), were then used to stimulate the immune system of the mice.


RESULTS
Approximately 50% of fetuses from hyperglycemic (>26 mM/liter blood glucose) dams were malformed, with neural tube defects predominating. Maternal immune stimulation during the time of normoglycemia, i.e., prior to the onset of hyperglycemia, was necessary to reduce teratogenic effects associated with hyperglycemia for each of the immune stimulants. The immune-stimulated diabetic mice then produced significantly lower and approximately equal numbers of malformed fetuses: CFA 20.9%, GM-CSF 23.3%, and IFN-gamma 13.9%.


CONCLUSIONS
These results suggest that mechanistically diverse forms of nonspecific immune activation result in protection against diabetes-related teratogenesis, but only if given prior to onset of hyperglycemia.
Punareewattana
Korawuth
K
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0442, USA.
Holladay
Steven D
SD
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D000013:Congenital Abnormalities / Q000276:immunology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D005260:Female; D005620:Freund's Adjuvant / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D001786:Blood Glucose; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005620:Freund's Adjuvant