Ventilator-induced lung injury is mediated, at least in part, by TNF-α. We determined the effect of a recombinant human soluble TNF receptor fusion protein (etanercept) on mechanical ventilation (MV)-induced changes in a murine ventilator-induced lung injury model. After pretreatment with etanercept or placebo, C57BI/6 mice were anesthetized and randomized to MV with either low tidal volumes (VT, ∼7.5 mL/kg) or high VT(∼15 mLAg) for 5 h. Instrumented but spontaneously breathing mice served as controls. End points were lung wet-to-dry ratios, lung histopathology scores, protein levels, neutrophil cell counts and thrombin-antithrombin complex levels in bronchoalveolar lavage fluid (BALF), and cytokine levels in lung homogenates. The number of caspase 3-positive cells was used as a measure for apoptosis. Etanercept treatment attenuated MV-induced changes, in particular, in MV with high VT. Compared with placebo, etanercept reduced the number of neutrophils in BALF and thrombin-antithrombin complex levels in BALF and cytokine levels in lung homogenates. Lung wet-to-dry ratios, histopathology scores, and local protein levels in BALF, however, were not influenced by etanercept treatment. The number of caspase 3-positive cells was significantly higher in etanercept-treated animals. Inhibition of TNF by etanercept attenuates, in part, MV-induced changes.

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Keywords Adult respiratory distress syndrome, Artificial respiration, Pulmonary inflammation, Tidal volume, Ventilator-induced lung injury
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Journal Shock (Philadelphia)
Wolthuis, E.K, Vlaar, A.P.J, Choi, G, Roelofs, J.J.T.H, Haitsma, J.J, van Poll, T.D, … Schultz, M.J. (2009). Recombinant human soluble tumor necrosis factor-alpha receptor fusion protein partly attenuates ventilator-induced lung injury. Shock (Philadelphia), 31(3), 262–266. doi:10.1097/SHK.0b013e31817d42dd