Lung inflammatory responses to intratracheal interleukin-1alpha in ventilated preterm lambs

Interleukin-1alpha is an early response proinflammatory cytokine that has been associated with chorioamnionitis and preterm labor, brain injury, and bronchopulmonary dysplasia. However, IL-1alpha also can increase expression of surfactant proteins and induce lung maturation in the preterm fetus. We measured the effects of IL-1alpha given by intratracheal instillation (IT) and compared the responses with injection of i.v. IL-1alpha in surfactant-treated and ventilated premature lambs. IT recombinant ovine IL-1alpha at doses of 5 and 50 microg/kg caused a similar large recruitment of neutrophils into the bronchoalveolar lavage fluid. The neutrophils expressed CD11b, CD14, and CD44, but did not produce increased amounts of H(2)O(2). Cells from the bronchoalveolar lavage fluid had increased expression of proinflammatory cytokines, which also were increased in mRNA from lung tissue. The IT IL-1alpha also suppressed the expression of surfactant protein-C mRNA. Systemic effects were decreased neutrophils in blood, decreased lung function, increased heart rate, and hypotension or death in the 50 microg/kg IL-1alpha IT group and only decreased neutrophils in the blood in the 5 microg/kg IL-1alpha IT group. The i.v. IL-1alpha caused no lung inflammation or injury but did result in severe neutropenia and hypotension leading to early death. IT IL-1alpha can cause intense lung inflammation and systemic shock in ventilated preterm lungs.