Lung Inflammatory Responses to Intratracheal Interleukin-1α in Ventilated Preterm Lambs

N. Mulrooney, Alan Jobe, M. Ikegami

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    10 Citations (Scopus)


    Interleukin-1α 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 H2O2. 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.
    Original languageEnglish
    Pages (from-to)682-687
    JournalPediatric Research
    Issue number4
    Publication statusPublished - 2004

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