Publication

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

Wolthuis, E. K., Vlaar, A. P. J., Choi, G., Roelofs, J. J. T. H., Haitsma, J. J., van der Poll, T., Juffermans, N. P., Zweers, M. M. & Schultz, M. J., 2009, In : Shock. 31, 3, p. 262-6 5 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • 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

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
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

ID: 29061632