Evidence that cyclosporine treatment during pregnancy predisposes offspring to develop autoantibodies.
Cyclosporine was administered (11 mg/kg/day) to pregnant mice to study the effects of passively transferred CsA on the developing immune system. Placental transfer of CsA was shown by the detection of fetal-tissue levels ranging from 400 to 1500 ng CsA/g tissue. Treatment clearly altered the developing immune system. Thymuses from the day-18 embryos exposed to CsA were partially depleted of CD4+CD8- single positive cells. Eleven of 50 offspring born to CsA-treated mothers developed significant levels of IgG autoantibodies to gastric antigens. In addition, two animals that received CsA in utero developed an extensive mononuclear cell infiltrate in the gastric mucosa resembling autoimmune gastritis. These results raise the possibility that the administration of CsA during pregnancy may result in potential long-term effects on the developing immune system. Offspring of such pregnancies may suffer an increased incidence or severity of autoimmune diseases.
Classen
J B
JB
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Shevach
E M
EM
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000139:chemically induced; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D003524:Cyclosporins / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000276:immunology / Q000473:pathology; D005756:Gastritis / Q000139:chemically induced; D051379:Mice; D008809:Mice, Inbred C3H; D011247:Pregnancy; D013950:Thymus Gland / Q000187:drug effects
D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies; D015704:CD4 Antigens; D016827:CD8 Antigens; D003524:Cyclosporins