Intratracheal anti-tumor necrosis factor-alpha antibody attenuates ventilator-induced lung injury in rabbits

J Appl Physiol (1985). 1999 Aug;87(2):510-5. doi: 10.1152/jappl.1999.87.2.510.


To evaluate the role of tumor necrosis factor (TNF)-alpha in the pathogenesis of ventilator-induced lung injury, we 1) measured TNF-alpha production in the lung caused by conventional mechanical ventilation (CMV) and 2) evaluated the protective effect of anti-TNF-alpha antibody (Ab) in saline-lavaged rabbit lungs. After they received saline lung lavage, rabbits were intratracheally instilled with 1 mg/kg of polyclonal anti-TNF-alpha Ab in the high-dose group (n = 6), 0.2 mg/kg of anti-TNF-alpha Ab in the low-dose group (n = 6), serum IgG fraction in the Ab control group (n = 6), and saline in the saline control group (n = 7). Animals then underwent CMV for 4 h. Levels of TNF-alpha in lung lavage fluid were significantly higher after CMV than before in both control groups. Pretreatment with intratracheal instillation of high and low doses of anti-TNF-alpha Ab improved oxygenation and respiratory compliance, reduced the infiltration of leukocytes, and ameliorated pathological findings. CMV led to TNF-alpha production in the lungs, and intratracheal instillation of anti-TNF-alpha Ab attenuated CMV-induced lung injury in this model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Reaction / metabolism
  • Animals
  • Antibodies / pharmacology*
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Humans
  • Infant, Newborn
  • Intubation, Intratracheal
  • Lung / immunology
  • Lung / pathology
  • Lung Compliance / immunology
  • Lung Injury*
  • Macrophages / metabolism
  • Male
  • Neutrophils / metabolism
  • Oxygen / blood
  • Rabbits
  • Respiration, Artificial
  • Respiratory Distress Syndrome, Newborn / metabolism
  • Respiratory Distress Syndrome, Newborn / pathology
  • Respiratory Distress Syndrome, Newborn / therapy*
  • Trachea
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism*
  • Ventilators, Mechanical / adverse effects*


  • Antibodies
  • Tumor Necrosis Factor-alpha
  • Oxygen