Am. J. Respir. Crit. Care Med., Volume 164, Number 3, August 2001, 494-498

Effects of Ventilation with Different Positive End-expiratory Pressures on Cytokine Expression in the Preterm Lamb Lung

APURWA S. NAIK, SUHAS G. KALLAPUR, CINDY J. BACHURSKI, ALAN H. JOBE, JACEK MICHNA, BORIS W. KRAMER, and MACHIKO IKEGAMI

Children's Hospital Medical Center, Division of Pulmonary Biology, Cincinnati, Ohio

Ventilator-induced lung injury increases proinflammatory cytokines in the adult lung. We asked if positive end-expiratory pressure (PEEP) affects proinflammatory cytokine mRNA expression in the preterm lung. Preterm lambs at 129 ± 3 d gestation were treated with 100 mg/kg recombinant human surfactant protein-C surfactant and ventilated for 2 or 7 h with 0, 4, or 7 cm H₂O of PEEP. Unventilated fetal lambs were used as controls. Within 2 h of ventilation, alveolar total protein and activated neutrophils were increased and expression of mRNAs for the proinflammatory cytokines interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor- (TNF-) was increased in lung tissue of all ventilated animals relative to unventilated controls. Alveolar protein and neutrophils were higher for 0 and 7 PEEP animals than 4 PEEP animals. IL-1, IL-6, and IL-8 mRNAs were significantly elevated in animals ventilated with 0 PEEP compared with 4 PEEP. The percentage fractional area of collapsed alveoli was significantly higher for 0 PEEP compared with 4 and 7 PEEP groups. Mechanical ventilation increased the expression of proinflammatory mediators in surfactant-treated preterm lungs and the use of 4 PEEP minimized this response.

Keywords: inflammation; lung injury; bronchopulmonary dysplasia; respiratory distress syndrome

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