Abstract P094: Vasopressin Infusion in Mice During Pregnancy Results in Immune Alterations Consistent with Human Preeclampsia
The immediate and long-term maternal and fetal health complications of preeclampsia (PreE) have been linked to an aberrant T helper immune response and pro-inflammatory cytokine profile. AVP secretion is both stimulated by and stimulates pro-inflammatory cytokine secretion and activation of lymphocytes. Our AVP infusion mouse model of PreE closely replicates human PreE. The objective of this study was to investigate if AVP infusion induces the maternal-fetal immune alterations in PreE.
Immune responses were evaluated in wild-type C57BL/6 female mice chronically infused with AVP (24 ng/hr or saline s.c.) throughout pregnancy. By flow cytometry, we observed an increase in the frequency of IL-17 (1.2% vs. 2.6%, p<0.05), TNFα (0.9% vs. 1.6%, p<0.0001), and IFNγ (1.8% vs. 3.4%, p<0.05) expressing T cells in AVP dams. An increase in the frequency of IL-12 producing cells (1.0% vs. 2.4%, p<0.05) and elevated expression of co-stimulatory molecules on dendritic cells (DCs) from AVP dams suggested enhanced DC function. The maternal plasma revealed a significant reduction in IL-17 (7.1e+6 vs. 3.4e+5 ng/g, p<0.05) and IL-6 (3.4e+5 vs. 0.0 ng/g, p<0.01) production in AVP dams by ELISA as seen in human PreE. Pro-inflammatory TNFα was also significantly decreased in the maternal kidney of AVP dams (2.3e+9 vs. 1.3e+9 ng/g, p<0.05). IL-4 production was significantly reduced in the maternal kidney of AVP dams (5.7e+7 vs. 3.4+7 ng/g, p<0.05) suggesting a blunted Th2 response as seen in human PreE. AVP infusion did not result in alterations of cytokine production in the maternal liver, or fetal liver and kidney. Interestingly, IL-17 production was increased in the amniotic fluid (3.0e+6 vs. 1.3e+7 ng/g, p<0.05) and lower in the placenta (2.5e+7 vs. 1.3e+7 ng/g, p<0.0001) of AVP dams. IL-4 production was decreased in both the amniotic fluid (4.5e+5 vs. 2.0e+5 ng/g, p<0.05) and placenta (3.1e+6 vs. 2.0e+6 ng/g, p<0.05) of AVP dams again suggesting a lower Th2 response.
These data support our hypothesis that AVP induces maternal-fetal immune alterations consistent with human PreE. Ongoing experiments are aimed at identifying the lymphocytes and cytokines involved as well as local vs. systemic immune dysfunction induced by AVP in pregnancy.
Author Disclosures: S.M. Scroggins: None. D.A. Santillan: None. N.A. Pearson: None. J.A. Sangren: None. J.Y. Min: None. E.J. Devor: None. G.L. Pierce: None. K.K. Leslie: None. J.L. Grobe: None. M.K. Santillan: None.
This research has received full or partial funding support from the American Heart Association, National Center.
- © 2015 by American Heart Association, Inc.