Dose and time response after intraamniotic endotoxin in preterm lambs

Intraamniotic endotoxin causes chorioamnionitis, which is followed by impro ved 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 af ter 7 d. Four and 10 mg endotoxin caused similar lung maturation and inflam mation in the lung and chorioamnion. The number of neutrophils in cord bloo d and the inflammatory cells in alveolar lavage and fetal lung tissue incre ased in a dose-dependent manner. Lower endotoxin doses induced indicators o f chorioamnionitis, lung and systemic inflammation without inducing lung ma turation. Therefore, some degree of inflammation can occur without subseque nt 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 in flammation after intraamniotic endotoxin. At 5 h active inflammatory cells were in the airways producing hydrogen peroxide, and interleukin-6 and -8 w ere 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 ex posure to proinflammatory cytokines.