Effects of ventilation with different positive end-expiratory pressures on cytokine expression in the preterm lamb lung.
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.
Naik
A S
AS
Children's Hospital Medical Center, Division of Pulmonary Biology, Cincinnati, Ohio 45229, USA.
Kallapur
S G
SG
Bachurski
C J
CJ
Jobe
A H
AH
Michna
J
J
Kramer
B W
BW
Ikegami
M
M
D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation; D007385:Intermittent Positive-Pressure Ventilation; D011650:Pulmonary Alveoli / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D012127:Respiratory Distress Syndrome, Newborn / Q000503:physiopathology*; D012756:Sheep; D013501:Surface-Active Agents
D016207:Cytokines; D012333:RNA, Messenger; D013501:Surface-Active Agents