Maternal morbidity and mortality (MM) is increased in the setting of bacterial (pyelonephritis) and viral (influenza) infection. It remains unkown if alterations in the immune response could account for the increase in maternal mortality. We sought to determine if the systemic immune response is functionally different during the pregnant (P) and non-pregnant (NP) state.
A model of systemic inflammation with CD-1 mice in nonpregnant (NP) and pregnant (P, E15 and E18) was used. Three experiments: #1) Observational studies for MM #2) 6 hrs after administration of intraperitoneal (IP) LPS or saline, serum was collected and spleens harvested. ELISAs for Th 1and the Th 2 cytokines and CxCL 10, sE-selectin, s-ICAM were performed. IHC was performed on spleens for CD4,CD8,CD11b and CD11c. #3) Pseudo-preganant state was created with estradiol (E) and progesterone (P) (n=18).
NP administration of LPS did not cause mortality. LPS resulted 88% MM within 48 hrs on E15 and 100 % on E18. Systemic inflammation resulted in a potent cytokine response in both NP and P. Systemic inflammation in P but not NP results in increased staining for CD 8 (cytotoxic T-cells) and CD 11c (dendritic cells) in spleens. Pseudopregnant mice had increased MM from LPS compared to NP controls.
The potent cytokine response in both the NP and pregnant animals suggest that cytokines do not modulate the increase in maternal mortality. Altered T-cell and dendritic cell responses in pregnancy may be responsible for an increase in MM from systemic illness. E+P appear to directly mediate the altered immune response in pregnancy. Targeting the altered immune response may serve to decrease maternal mortality from systemic illnesses.
© 2008 Mosby, Inc. Published by Elsevier Inc. All rights reserved.