The response of the innate immune and cardiovascular systems to LPS in pregnant and nonpregnant mice
Autor: | Masao Takata, Mark R. Johnson, Lydia F Edey, James Leiper, Fabiana Gordon, Julia Zöllner, Kieran P. O'Dea, Laura G. Howe |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Lipopolysaccharides medicine.medical_specialty Lipopolysaccharide innate immune system Biology Cardiovascular System Sepsis sepsis 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Immune system Internal medicine medicine Animals RNA Messenger Obstetrics & Reproductive Medicine Inflammation 030219 obstetrics & reproductive medicine Lung Electrical impedance myography Monocyte blood pressure Cell Biology General Medicine 11 Medical And Health Sciences 06 Biological Sciences medicine.disease Immunity Innate 030104 developmental biology medicine.anatomical_structure Endocrinology Blood pressure Reproductive Medicine chemistry Gene Expression Regulation Female pregnancy Ex vivo Biomarkers |
Popis: | 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. |
Databáze: | OpenAIRE |
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