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

Abstract

To evaluate the role of tumor necrosis factor (TNF)-α in the pathogenesis of ventilator-induced lung injury, we 1) measured TNF-α production in the lung caused by conventional mechanical ventilation (CMV) and 2) evaluated the protective effect of anti-TNF-α 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-α Ab in the high-dose group ( n = 6), 0.2 mg/kg of anti-TNF-α 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-α 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-α Ab improved oxygenation and respiratory compliance, reduced the infiltration of leukocytes, and ameliorated pathological findings. CMV led to TNF-α production in the lungs, and intratracheal instillation of anti-TNF-α Ab attenuated CMV-induced lung injury in this model.