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

TNF-α has been associated with chorioamnionitis and the subsequent development of bronchopulmonary dysplasia in preterm infants. We asked whether bioactive recombinant ovine TNF-α could induce chorioamnionitis, lung inflammation, lung maturation, and systemic effects in fetal sheep. We compared the responses to IL-1α, a cytokine known to induce these responses in preterm sheep. Intra-amniotic TNF-α 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-1α induced inflammation and lung maturation. TNF-α 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-1α caused a systemic inflammatory response in fetal sheep, whereas there was no fetal response to intravascular TNF-α. Fetal and newborn preterm sheep are minimally responsive to TNF-α. Therefore, the presence of a mediator such as TNF-α in a developing animal does not necessarily mean that it is causing the responses anticipated from previous results in adult animals.