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

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.

• Authors: 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
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 31 Issue 3 Pg. 262-6 (Mar 2009) ISSN: 1540-0514 [Electronic] United States
• PMID: 18650784 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Immunoglobulin G
• Receptors, Tumor Necrosis Factor
• Recombinant Fusion Proteins
• Tumor Necrosis Factor-alpha
• Casp3 protein, mouse
• Caspase 3
• Etanercept

Topics

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