417: Is the host immune response to localized inflammation different in pregnancy?

Abstract

PREGNANCY? JUAN M. GONZALEZ, ELLA OFORI, MICHAL ELOVITZ, Hospital of the University of Pennsylvania, Obstetrics and Gynecology Division of Maternal-Fetal Medicine, Philadelphia, Pennsylvania, University of Pennsylvania, , Pennsylvania OBJECTIVE: Pregnancy has long been assumed to be a state of immunosupression. Data from our lab demonstrated that the innate immune response is upregulated in maternal tissues during pregnancy. Understanding the response and regulation of the host immune response in pregnancy compared to non-pregnant is essential if disruptions in the immune response are significant contributors to adverse obstetrical outcomes. The studies sought to assess whether the systemic immune response to localized inflammation was divergent between non-pregnant (NP) and pregnant (P) animals. STUDY DESIGN: CD-1 timed (P) and (NP) mice were used. P (E15) and NP were randomized to (n 8 per group) to 3 groups: 1) Controls: no treatment 2) Saline: anesthesia, surgery and intrauterine (IU) infusion of saline, and 3) Lipopolysaccharide (LPS): anesthesia, surgery and IU of LPS. 6 hours after IU infusion, maternal blood was collected from the inferior vena cava. ELISAs were performed for TH1/ TH2 cytokines (IL-10,IL-6, IL-12, TNF-alpha) and early markers of endothelial and leukocyte activation (CXCL10, sE-Selectin, sICAM). RESULTS: Baseline levels for the cytokines and markers studied were not significantly different between NP and P mice. LPS up-regulated the immune response in both the NP and P. The response to IU inflammation in P evoked a significantly higher systemic release of cytokine IL-6 than in NP (P 0.001). The fold change for cytokines and markers in LPS/control was higher in the P state compared to the NP (see table). CONCLUSION: The response to localized IU inflammation is modulated during pregnancy with differing TH1 and early endothelial activation compared to NP. Understanding the differential immune response in pregnancy may provide insight into adverse obstetrical outcomes associated with inflammation as well as provide potential therapeutic targets.