Intratracheal anti-tumor necrosis factor-alpha antibody attenuates ventilator-induced lung injury in rabbits.
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.
Imai
Y
Y
Pathophysiology Research Laboratory, National Children's Medical Research Center, Tokyo, 154-8509, 142-8555 Japan.
Kawano
T
T
Iwamoto
S
S
Nakagawa
S
S
Takata
M
M
Miyasaka
K
K
D000210:Acute-Phase Reaction / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D006801:Humans; D007231:Infant, Newborn; D007442:Intubation, Intratracheal; D008168:Lung / Q000276:immunology / Q000473:pathology; D008170:Lung Compliance / Q000276:immunology; D055370:Lung Injury; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D011817:Rabbits; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014132:Trachea; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*; D012122:Ventilators, Mechanical / Q000009:adverse effects*
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen