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in Preterm Sheep
1 Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
2 University of Western Australia, School of Women's and Infants' Health, Perth, Western Australia, Australia
* To whom correspondence should be addressed. E-mail: machiko.ikegami{at}cchmc.org.
TNF
has been associated with chorioamnionitis and the subsequent development of bronchopulmonary dysplasia in preterm infants. We asked if bioactive recombinant ovine TNF could induce chorioamnionitis, lung inflammation, lung maturation, and systemic effects in fetal sheep. We compared the responses to IL-1 , a cytokine known to induce these responses in preterm sheep. Intra-amniotic TNF caused no chorioamnionitis, no lung maturation and a very small increase in inflammatory cells in the fetal lung after 5h, 2d and 7d. In contrast, IL-1 induced inflammation and lung maturation. TNF given into the airways at birth increased granulocytes in the bronchoalveolar lavage fluid of ventilated preterm lungs and decreased the mRNA for SP-C but did not adversely effect postnatal lung function. An intravascular injection of IL-1 caused a systemic inflammatory response in fetal sheep while there was no fetal response to intravascular TNF. Fetal and newborn preterm sheep are minimally responsive to TNF. Therefore, the presence of a mediator such as TNF in a developing animal does not necessarily mean that it is causing the responses anticipated from previous results in adult animals.
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