Lung Inflammatory Responses to Intratracheal Interleukin-α in Ventilated Preterm Lambs

Abstract

Interleukin-1 a is an early response proinflammatory cytokine that has been associated with chorioamnionitis and preterm labor, brain injury, and bronchopulmonary dysplasia. However, IL-1α also can increase expression of surfactant proteins and induce lung maturation in the preterm fetus. We measured the effects of IL-1α given by intratracheal instillation (IT) and compared the responses with injection of i.v. IL-1α in surfactant-treated and ventilated premature lambs. IT recombinant ovine IL-1α at doses of 5 and 50 μg/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 2O2. Cells from the bronchoalveolar lavage fluid had increased expression of proinflammatory cytokines, which also were increased in mRNA from lung tissue. The IT IL-1α 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 μg/kg IL-1α IT group and only decreased neutrophils in the blood in the 5 μg/kg IL-1α IT group. The i.v. IL-1α caused no lung inflammation or injury but did result in severe neutropenia and hypotension leading to early death. IT IL-1α can cause intense lung inflammation and systemic shock in ventilated preterm lungs.