Enhanced pulmonary response to inhaled endotoxin in pregnant rats.
Huffman-LJ; Prugh-DJ; Brumbaugh-K; Frazer-DG; Reynolds-JS; Goldsmith-WT
Am J Respir Crit Care Med 2003 Apr; 167(7):A973
Evidence suggests that pregnant animals are more sensitive than non-pregnant animals to the systemic administration of endotoxin. In this study, we assessed whether an enhanced sensitivity of the pulmonary system to aerosolized endotoxin might exist during pregnancy. Pregnant rats (17 days gestation) or age-matched virgin rats were exposed to air or endotoxin (lipopolysaccharide; 126,000 +/- 21,000 EU/cubic meter) by inhalation for 3 hours and pulmonary inflammatory responses were evaluated. Breathing rates, tidal volumes, minute ventilation, and serum corticosterone levels were measured. In vitro experiments were performed to determine the effects of endotoxin on the release of reactive oxygen/nitrogen species and cytokines by alveolar macrophages (AMs) from virgin or pregnant rats. At 18 hours following endotoxin, bronchoalveolar lavage (BAL) lactate dehydrogenase activities in pregnant rats were 15-fold greater than those in virgin rats. BAL polymorphonuclear leukocyte numbers were also two-fold greater in pregnant rats than virgins following the inhalation of endotoxin. These results indicate that an increased pulmonary inflammatory response to endotoxin occurs during pregnancy in rats. Additional findings suggest that these pregnancy-linked pulmonary responses to endotoxin cannot be explained by changes in the inhaled dose of endotoxin, differences in corticosterone levels or alterations in the response of AMs to endotoxin. To our knowledge this is the first study which .has evaluated pulmonary responses to inhaled endotoxin during pregnancy. Our finding that pregnancy is associated with an increased sensitivity of the pulmonary system to endotoxin raises the possibility that there is a generalized enhancement of pulmonary responses to inhaled toxic agents during pregnancy.
Laboratory-animals; Animal-studies; Animals; Endotoxins; Aerosols; In-vitro-studies; Alveolar-cells; Leukocytes; Inhalants; Inhalation-studies; Toxins; Pulmonary-system-disorders; Reproductive-effects; Reproductive-hazards
Abstract; Conference/Symposia Proceedings
Disease and Injury: Fertility and Pregnancy Abnormalities
American Journal of Respiratory and Critical Care Medicine, 2003 International Conference, The American Thoracic Society, Seattle, WA, May 16-21, 2003