Abstract 286: Immune Dysfunction in a Vasopressin-Induced Mouse Model of Preeclampsia
Preeclampsia is a disease of pregnancy and the postpartum period, affecting 5-7% of all U.S. pregnancies. We recently determined that elevated secretion of arginine vasopressin (AVP) in humans is detected as early as the 6th week of pregnancy in the women that subsequently develop preeclampsia. Further, we have determined that in C57BL/6 mice, chronic AVP infusion serves as a clinically-relevant and pregnancy-specific model of preeclampsia. Although the pathogenesis of preeclampsia is still poorly understood, an inflammatory immune response is clearly involved. AVP secretion is stimulated by proinflammatory cytokines and AVP in turn can act upon receptors present on lymphocytes. We hypothesize that hypersecretion of AVP results in maternal-fetal immune alterations in preeclamptics. Immune responses were evaluated in wild-type C57BL/6 female mice chronically infused with AVP (24 ng/hr or saline s.c.) throughout pregnancy. We observed an increase in the frequency of IL-12 (saline N=7: 1.1±0.2, vs AVP N=9: 2.2±0.4, P<0.05), IL-17 (saline N=7: 1.2±0.17, vs AVP N=9: 2.6±0.4, P<0.05) and TNFa (saline N=8: 0.9±0.1, vs AVP N=9: 1.6±0.1, P<0.005) expressing lymphocytes isolated from AVP mice. Additionally, the frequency of IFNg expressing lymphocytes was increased in AVP mice, approaching statistical significance (saline N=8: 2.2±0.9, vs AVP N=9: 3.0±0.4, P=0.059). The frequency of IL-6, IL-10, and LAP expressing splenic lymphocytes were similar between saline vs. AVP mice. Interestingly, maternal plasma revealed a significant reduction in IL-17 (saline N=4: 1.0e+7±3.8e+6, vs AVP N=5: 3.1e=5±1.3e+5 ng/g, P<0.05) in AVP mice. Neither IL-4 nor IFNg were detectable in maternal plasma of either group. Additionally, IL-17 trended higher in the amnionic fluid and lower in the placenta of AVP mice. IL-4 production trended lower in both the placenta and amnionic fluid of AVP-infused mice, while IFNg was similar between groups. These data support our hypothesis that AVP hypersecretion results in the maternal-fetal immune alterations associated with the development of preeclampsia. Ongoing experiments are aimed at identifying the lymphocytes and cytokines involved as well as local vs. systemic immune dysfunction associated with AVP-induced preeclampsia.
Author Disclosures: S.M. Scroggins: None. D.A. Santillan: None. J.Y. Min: None. J.A. Sangren: None. N.A. Pearson: None. K.N. Gibson-Corley: 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.
- © 2014 by American Heart Association, Inc.