Maternal immune stimulation alters cytokines during pregnancy

Environmental teratogens are the main cause of post‐conception birth defects. Non‐specific stimulation of the maternal immune system can prevent fetal malformation but the mechanism underlying this protection is unknown. Modulation of fetal development by immunoregulatory cytokines is one possible mechanism. To test this hypothesis, a murine model of valproic acid induced neural tube defects was used to determine changes in cytokine concentrations throughout gestation. Both Th1 (TNFα, IFNγ) and Th2 (IL‐6, IL‐10, GM‐CSF) cytokine concentrations were determined in control, teratogen‐exposed and immune stimulated tertatogen‐exposed mice. IFN‐γ was used to stimulate dams 10 and 5 days prior to breeding and teratogen was administered on day 8 of gestation. Serum cytokine concentrations were measured at eleven time intervals before and during gestation. Pre‐breeding immune stimulation altered most cytokine concentrations throughout pregnancy compared to controls. When mice were exposed to teratogen, immune stimulated dams significantly altered TNFα, IL‐10 and GM‐CSF concentrations. Thus these cytokines may be involved in the mechanism by which maternal immune stimulation confers protection against fetal malformation. This work was funded through the Harvey Peter's Foundation, and NIH‐NCRR K01RR16241.