Dose and time response after intraamniotic endotoxin in preterm lambs.

Abstract

Intraamniotic endotoxin causes chorioamnionitis, which is followed by improved fetal lung function after 4 d in fetal sheep. We evaluated 0.1 mg, 1 mg, 4 mg, and 10 mg endotoxin for inflammation and lung maturation effects after 7 d. Four and 10 mg endotoxin caused similar lung maturation and inflammation in the lung and chorioamnion. The number of neutrophils in cord blood and the inflammatory cells in alveolar lavage and fetal lung tissue increased in a dose-dependent manner. Lower endotoxin doses induced indicators of chorioamnionitis, lung and systemic inflammation without inducing lung maturation. Therefore, some degree of inflammation can occur without subsequent lung maturation. The inflammatory changes caused by 4 mg endotoxin were assessed after 5 h, 24 h, 72 h, and 7 d to discern local versus systemic inflammation after intraamniotic endotoxin. At 5 h active inflammatory cells were in the airways producing hydrogen peroxide, and interleukin-6 and -8 were increased in the cord blood indicating both lung and systemic responses. Cells recruited into the amniotic fluid produced proinflammatory cytokine mRNA for 7 d with no cytokine mRNA in chorioamnion, lung, or spleen after 72 h. The cells in the amniotic fluid may be a source of prolonged fetal exposure to proinflammatory cytokines.

• Authors: B W Kramer, T J Moss, K E Willet, J P Newnham, P D Sly, S G Kallapur, M Ikegami, A H Jobe
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 164 Issue 6 Pg. 982-8 (Sep 15 2001) ISSN: 1073-449X [Print] United States
• PMID: 11587983 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cytokines
• Endotoxins
• Interleukin-6
• Interleukin-8
• Pulmonary Surfactants
• RNA, Messenger

Topics

• Amniotic Fluid (cytology)
• Animals
• Animals, Newborn
• Bronchoalveolar Lavage Fluid (cytology)
• Bronchopulmonary Dysplasia (immunology, physiopathology, prevention & control)
• Chorioamnionitis (etiology, physiopathology)
• Cytokines (genetics, physiology)
• Data Interpretation, Statistical
• Disease Models, Animal
• Endotoxins (administration & dosage)
• Enzyme-Linked Immunosorbent Assay
• Female
• Fetal Blood (cytology)
• Humans
• Infant, Newborn
• Inflammation (immunology, physiopathology)
• Interleukin-6 (physiology)
• Interleukin-8 (physiology)
• Male
• Neutrophils (physiology)
• Pregnancy
• Pulmonary Surfactants (chemistry, physiology)
• RNA, Messenger (analysis)
• Random Allocation
• Respiratory Distress Syndrome, Newborn (immunology, physiopathology, prevention & control)
• Sheep
• Time Factors