TY - JOUR
T1 - Recombinant human soluble tumor necrosis factor-alpha receptor fusion protein partly attenuates ventilator-induced lung injury
AU - Wolthuis, Esther K.
AU - Vlaar, Alexander P.J.
AU - Choi, Goda
AU - Roelofs, Joris J.T.H.
AU - Haitsma, Jack J.
AU - Van Poll, Tom Der
AU - Juffermans, Nicole P.
AU - Zweers, Machteid M.
AU - Schultz, Marcus J.
PY - 2009/3
Y1 - 2009/3
N2 - 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 (V T, ∼7.5 mL/kg) or high V T (∼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 V T. 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.
AB - 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 (V T, ∼7.5 mL/kg) or high V T (∼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 V T. 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.
KW - Adult respiratory distress syndrome
KW - Artificial respiration
KW - Pulmonary inflammation
KW - Tidal volume
KW - Ventilator-induced lung injury
UR - http://www.scopus.com/inward/record.url?scp=62449287549&partnerID=8YFLogxK
U2 - https://doi.org/10.1097/SHK.0b013e31817d42dd
DO - https://doi.org/10.1097/SHK.0b013e31817d42dd
M3 - Article
C2 - 18650784
SN - 1073-2322
VL - 31
SP - 262
EP - 266
JO - Shock
JF - Shock
IS - 3
ER -