Minimal lung and systemic responses to TNF-alpha in preterm sheep

Machiko Ikegami, Timothy Moss, Suhas Kallapur, Neil Mulrooney, Boris Kramer, Ilias Nitsos, Cindy Bachurski, John Newnham, Alan Jobe

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TNF-alpha has been associated with chorioamnionitis and the subsequent development of bronchopulmonary dysplasia in preterm infants. We asked whether bioactive recombinant ovine TNF-alpha could induce chorioamnionitis, lung inflammation, lung maturation, and systemic effects in fetal sheep. We compared the responses to IL-1alpha, a cytokine known to induce these responses in preterm sheep. Intra-amniotic TNF-alpha caused no chorioamnionitis, no lung maturation, and a very small increase in inflammatory cells in the fetal lung after 5 h, 2 days (d), and 7 d. In contrast, IL-1alpha induced inflammation and lung maturation. TNF-alpha given into the airways at birth increased granulocytes in the bronchoalveolar lavage fluid of ventilated preterm lungs and decreased the mRNA for surfactant protein C but did not adversely effect postnatal lung function. An intravascular injection of IL-1alpha caused a systemic inflammatory response in fetal sheep, whereas there was no fetal response to intravascular TNF-alpha. Fetal and newborn preterm sheep are minimally responsive to TNF-alpha. Therefore, the presence of a mediator such as TNF-alpha in a developing animal does not necessarily mean that it is causing the responses anticipated from previous results in adult animals.
Original languageEnglish
Pages (from-to)121 - 129
Number of pages9
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number1
Publication statusPublished - 2003
Externally publishedYes

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