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J Appl Physiol 87: 510-515, 1999;
8750-7587/99 $5.00
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Vol. 87, Issue 2, 510-515, August 1999

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

Yumiko Imai1, Toshio Kawano1, Sanju Iwamoto2, Satoshi Nakagawa1, Masao Takata1, and Katsuyuki Miyasaka1

1 Pathophysiology Research Laboratory, National Children's Medical Research Center, Tokyo, 154-8509; and 2 Division of Biochemistry, Showa University School of Medicine, Tokyo, 142-8555 Japan

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.

conventional mechanical ventilation; intratracheal instillation


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