Recombinant human soluble tumor necrosis factor-alpha receptor fusion protein partly attenuates ventilator-induced lung injury

Esther K Wolthuis, Alexander P J Vlaar, Goda Choi, Joris J T H Roelofs, Jack J Haitsma, Tom van der Poll, Nicole P Juffermans, Machteld M Zweers, Marcus J Schultz

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    Abstract

    Ventilator-induced lung injury is mediated, at least in part, by TNF-alpha. 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, C57Bl/6 mice were anesthetized and randomized to MV with either low tidal volumes (VT, approximately 7.5 mL/kg) or high VT ( approximately 15 mL/kg) 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.

    Original languageEnglish
    Pages (from-to)262-6
    Number of pages5
    JournalShock
    Volume31
    Issue number3
    DOIs
    Publication statusPublished - 2009

    Keywords

    • Animals
    • Anti-Inflammatory Agents, Non-Steroidal
    • Bronchoalveolar Lavage Fluid
    • Caspase 3
    • Disease Models, Animal
    • Etanercept
    • Female
    • Humans
    • Immunoglobulin G
    • Lung
    • Mice
    • Receptors, Tumor Necrosis Factor
    • Recombinant Fusion Proteins
    • Tumor Necrosis Factor-alpha
    • Ventilator-Induced Lung Injury

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