The response of the innate immune and cardiovascular systems to LPS in pregnant and nonpregnant mice

• Published in: Biology of reproduction 2017-08, Vol.97 (2), p.258-272
• Main Authors: Zöllner, Julia, Howe, Laura G, Edey, Lydia F, O'Dea, Kieran P, Takata, Masao, Gordon, Fabiana, Leiper, James, Johnson, Mark R
• Format: Article
• Language: English
• Subjects: Animals; Aorta; Apoptosis; Biomarkers; Blood Pressure; Cardiovascular System - drug effects; Cytokines; DNA probes; Endotoxemia; Female; Flow cytometry; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; Immune response; Immunity, Innate - drug effects; Inflammation; Inflammation - chemically induced; Inflammation - pathology; innate immune system; Leukocytes (neutrophilic); Lipopolysaccharides; Lipopolysaccharides - toxicity; Mice; Monocytes; PREGNANCY; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sepsis; Vasoactive agents
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1093/biolre/iox076

Sepsis is the leading cause of direct maternal mortality, but there are no data directly comparing the response to sepsis in pregnant and nonpregnant (NP) individuals. This study uses a mouse model of sepsis to test the hypothesis that the cardiovascular response to sepsis is more marked during pregnancy. Female CD1 mice had radiotelemetry probes implanted and were time mated. NP and day 16 pregnant CD-1 mice received intraperitoneal lipopolysaccharide (LPS; 10 μg, serotype 0111: B4). In a separate study, tissue and serum (for RNA, protein and flow cytometry studies), aorta and uterine vessels (for wire myography) were collected after LPS or vehicle control administration. Administration of LPS resulted in a greater fall in blood pressure in pregnant mice compared to NP mice. This occurred with similar changes in the circulating levels of cytokines, vasoactive factors, and circulating leukocytes, but with a greater monocyte and lesser neutrophil margination in the lungs of pregnant mice. Baseline markers of cardiac dysfunction and apoptosis as well as cytokine expression were higher in pregnant mice, but the response to LPS was similar in both groups as was the ex vivo assessment of vascular function. In pregnant mice, nonfatal sepsis is associated with a more marked hypotensive response but not a greater immune response. We conclude that endotoxemia induces a more marked hypotensive response in pregnant compared to NP mice. These changes were not associated with a more marked systemic inflammatory response in pregnant mice, although monocyte lung margination was greater. The more marked hypotensive response to LPS may explain the greater vulnerability to some infections exhibited by pregnant women. Summary Sentence In pregnant mice, nonfatal sepsis is associated with a more marked hypotensive response but not a greater immune response.