Effects of ventilation with different positive end-expiratory pressures oncytokine expression in the preterm lamb lung

Ventilator-induced lung injury increases proinflammatory cytokines in the a dult lung. We asked if positive end-expiratory pressure (PEEP) affects proi nflammatory cytokine mRNA expression in the preterm lung. Preterm lambs at 129 +/- 3 d gestation were treated with 100 mg/kg recombinant human surfact ant 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 ven tilation, alveolar total protein and activated neutrophils were increased a nd expression of mRNAs for the proinflammatory cytokines interleukin (IL)-1 beta, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) was increase d in lung tissue of all ventilated animals relative to unventilated control s. Alveolar protein and neutrophils were higher for 0 and 7 PEEP animals th an 4 PEEP animals. IL-1 beta IL-6, and IL-8 mRNAs were significantly elevat ed in animals ventilated with 0 PEEP compared with 4 PEEP. The percentage f ractional area of collapsed alveoli was significantly higher for 0 PEEP com pared with 4 and 7 PEEP groups. Mechanical ventilation increased the expres sion of proinflammatory mediators in surfactant-treated preterm lungs and t he use of 4 PEEP minimized this response.