Recruited inflammatory cells mediate endotoxin-induced lung maturation in preterm fetal lambs

Am J Respir Crit Care Med. 2005 Nov 15;172(10):1315-21. doi: 10.1164/rccm.200506-1007OC. Epub 2005 Aug 18.


Rationale: Chorioamnionitis is paradoxically associated with a decreased incidence of respiratory distress syndrome in preterm infants. In preterm lambs, intraamniotic endotoxin and interleukin 1 (IL-1) induce lung inflammation followed by lung maturation.

Objective: To test if inflammatory cells are required to mediate induced lung maturation.

Methods: Lung inflammation was induced by intraamniotic injection of endotoxin or IL-1. Inflammatory cell recruitment to the lung was inhibited by an anti-CD18 blocking antibody given intramuscularly to the fetus. Preterm lambs were delivered at 124-d gestation (term = 150 d) 2 or 7 d after exposure to endotoxin/IL-1 or endotoxin/IL-1 + anti-CD18 antibody.

Measurements: Lung inflammation was measured by bronchoalveolar lavage fluid cell count, inflammatory scoring of lung parenchyma, and expression of proinflammatory cytokines and inducible nitric oxide synthase. Lung maturation was quantitated by surfactant protein mRNA expression, saturated phosphatidylcholine pool size, and pressure-volume curves.

Main results: Inhibition of CD18 significantly reduced endotoxin-induced but not IL-1-induced fetal lung inflammatory cell recruitment and activation as well as expression of proinflammatory cytokines. Compared with control lungs, both endotoxin and IL-1 induced lung maturation. Anti-CD18 antibody administration inhibited only endotoxin-induced but not IL-1-induced increases in surfactant protein mRNA and surfactant saturated phosphatidylcholine. Exposure to anti-CD18 antibody moderated endotoxin-induced increases in lung volumes but had no effect on IL-1-induced increases in lung volumes.

Conclusions: (1) Endotoxin- but not IL-1-induced inflammatory cell recruitment in the preterm fetal lamb lung is CD18 dependent; (2) recruited inflammatory cells mediate some aspects of fetal lung maturation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid
  • CD18 Antigens / immunology
  • Endotoxins
  • Female
  • Fetal Organ Maturity
  • Flow Cytometry
  • Interleukin-1 / analysis
  • Leukocyte Count
  • Lung / embryology*
  • Neutrophil Activation
  • Neutrophil Infiltration / drug effects
  • Nitric Oxide Synthase Type II / analysis
  • Pregnancy
  • Premature Birth
  • Pulmonary Surfactants / analysis
  • RNA, Messenger / analysis
  • Sheep


  • CD18 Antigens
  • Endotoxins
  • Interleukin-1
  • Pulmonary Surfactants
  • RNA, Messenger
  • Nitric Oxide Synthase Type II