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Skip Navigation LinksHome > March 2009 - Volume 31 - Issue 3 > RECOMBINANT HUMAN SOLUBLE TUMOR NECROSIS FACTOR-ALPHA RECEPT...
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doi: 10.1097/SHK.0b013e31817d42dd
Basic Science Aspects

RECOMBINANT HUMAN SOLUBLE TUMOR NECROSIS FACTOR-ALPHA RECEPTOR FUSION PROTEIN PARTLY ATTENUATES VENTILATOR-INDUCED LUNG INJURY

Wolthuis, Esther K.*†‡; Vlaar, Alexander P. J.*‡; Choi, Goda*‡§; Roelofs, Joris J. T. H.; Haitsma, Jack J.∥**; van der Poll, Tom§††‡‡; Juffermans, Nicole P.*‡; Zweers, Machteld M.; Schultz, Marcus J.*‡§§

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Abstract

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, C57Bl/6 mice were anesthetized and randomized to MV with either low tidal volumes (VT, ∼7.5 mL/kg) or high VT (∼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.

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