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A2985 - The Effects of Pregnancy on the Pulmonary Response to Lipopolysaccharide-Induced Acute Lung Injury
Author Block: R. E. Rieck1, L. R. Hoyt2, J. J. Bivona2, M. Kokoszynska2, S. Ventrone2, M. J. Porto2, E. A. Bonney1, B. T. Suratt2; 1Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Vermont Medical Center, Burlington, VT, United States, 2Department of Medicine, University of Vermont College of Medicine, Burlington, VT, United States.
Rationale
Acute respiratory distress syndrome (ARDS) in pregnancy occurs in 59.6 out of 100,000 live births and is associated with a 9% mortality rate. The effect of pregnancy on ARDS pathogenesis is not well understood. We hypothesized that pregnancy augments the immune response to lung injury. To begin to address this question, we adapted a model of LPS-induced lung injury to pregnancy.
Methods
Six week old C57BL/6 female mice were timed-mated with same-strain males under specific pathogen free conditions and normal light-dark cycles. On gestational day 16, the pregnant mice, along with age-matched non-pregnant control female mice, were exposed to nebulized LPS (3 mg/ml) for 15 minutes. At 24 hours, the mice were euthanized and bronchoalveolar lavage (BAL) fluid, lung tissue, and blood were collected. BAL cell counts were determined. BAL albumin levels were measured by Western blot. The results were quantified using densitometry. Whole lung cytokine IL-6, keratinocyte cytokine (KC), TNF-α, and monocyte chemotactic protein (MCP)-1 mRNA levels were assessed using quantitative real-time PCR.
Results
The pregnant mice had higher total cell counts (3.5x106 vs 2.2x106, p=0.04) and neutrophil counts (3.3x106 vs 2.0x106, p=0.03) than nonpregnant mice. Neither BAL albumin levels nor whole-lung IL-6, KC, MCP-1, or TNF-α levels were significantly different. There was no evidence of either pregnancy resorption nor preterm delivery. The pregnant mice had an average litter size of 6.5 ± 1.7 pups with no apparent resorbed pups.
Conclusions
Pregnant mice have increased airspace neutrophilia in response to LPS as compared to nonpregnant mice. However, the cytokine response and alveolar capillary membrane injury is not augmented. Pregnancy is associated with increased peripheral neutrophilia which may, in part, account for the differences in airspace neutrophilia that we found.
Supported by the Mead Fund and the Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont College of Medicine