TRACHEAL INSUFFLATION OF TUMOR-NECROSIS-FACTOR PROTECTS RATS AGAINST OXYGEN-TOXICITY

Tracheal insufflation of tumor necrosis factor (TNF; 5 μg or 1.2 x 105 U) markedly enhanced the survival of adult rats exposed to 100% O2: 12 of 17 rats (71%) survived for >11 days, whereas 30 of 30 controls (Hanks' balanced salt solution) insufflated rats (100%) died within 3 days of O2 exposure. Insufflation of γ-interferon (5 μg) or intraperitoneal injection of up to 40 μg TNF did not afford any protection. At 55 h after O2 exposure, TNF-insufflated rats showed less pulmonary edema, as determined by the extravascular lung water content-to-bloodless lung dry weight ratio and less alveolar capillary leak as determined by the protein content in the bronchoalveolar lavage fluid, than control insufflated rats similarly exposed. This protection against O2 toxicity by TNF insufflation was associated with increased lung superoxide dismutase, catalase, and glutathione peroxidase activities. The enhancement of lung antioxidant enzyme activities was noted at 55 h of O2 exposure, when control animals began to die of O2 toxicity. This temporal relationship suggests that TNF-induced increase in antioxidant enzyme activities contributes, at least in part, to the observed protection.