Minimal lung and systemic responses to TNF- in preterm sheep

Ikegami, Machiko, Timothy J. M. Moss, Suhas G. Kallapur, Neil Mulrooney, Boris W. Kramer, Ilias Nitsos, Cindy J. Bachurski, John P. Newnham, and Alan H. Jobe. Minimal lung and systemic responses to TNFin preterm sheep. Am J Physiol Lung Cell Mol Physiol 285: L121–L129, 2003. First published February 28, 2003; 10.1152/ajplung.00393.2002.—TNFhas been associated with chorioamnionitis and the subsequent development of bronchopulmonary dysplasia in preterm infants. We asked whether bioactive recombinant ovine TNFcould 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 TNFcaused 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-1 induced inflammation and lung maturation. TNFgiven 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-1 caused a systemic inflammatory response in fetal sheep, whereas 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 TNFin a developing animal does not necessarily mean that it is causing the responses anticipated from previous results in adult animals.