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

Am J Respir Crit Care Med. 2001 Aug 1;164(3):494-8. doi: 10.1164/ajrccm.164.3.2010127.


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 H(2)O 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)-1beta, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) 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-1beta, 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cytokines / pharmacology*
  • Disease Models, Animal
  • Humans
  • Infant, Newborn
  • Inflammation
  • Intermittent Positive-Pressure Ventilation*
  • Pulmonary Alveoli / physiology
  • RNA, Messenger / biosynthesis
  • Random Allocation
  • Respiratory Distress Syndrome, Newborn / physiopathology*
  • Sheep
  • Surface-Active Agents


  • Cytokines
  • RNA, Messenger
  • Surface-Active Agents