Early subcutaneous administration of etanercept (Enbrel) prevents from hyperoxia-induced lung injury.
Both hyperoxia-induced proapoptotic sensitization of alveolar type II cells (TII cells) and high-stretch mechanical ventilation induced pulmonary inflammation are tumor necrosis factor alpha (TNFalpha) mediated. Therefore, binding of free TNFalpha should protect from TNFalpha-mediated acute lung injury and ameliorate the subsequently developing chronic lung disease. Here, the authors show that a single subcutaneous pretreatment of rat with etanercept, a recombinant p75 TNF receptor 2 human immunoglobulin G1 (IgG1) construct, inhibits the hyperoxia-induced and TNFalpha-mediated increase in the expression of TNFalpha receptor, the activation of caspase 3 in TII cells, and, as an early indicator of lung injury, the capillary-alveolar leakage and granulocyte number in lung lavage. The authors assume that subcutaneous administration of etanercept might be suitable to prevent acute lung injury and its sequelae induced by hyperoxic ventilation of premature neonates and critically ill patients.
Guthmann
Florian
F
Klinik für Neonatologie, Charité Universitätsmedizin Berlin, Berlin, Germany.
Wissel
Heide
H
Rüstow
Bernd
B
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002199:Capillary Permeability; D053148:Caspase 3 / Q000378:metabolism; D000068800:Etanercept; D006098:Granulocytes; D018496:Hyperoxia / Q000150:complications*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D055370:Lung Injury / Q000517:prevention & control*; D011650:Pulmonary Alveoli / Q000098:blood supply; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000235:genetics / Q000627:therapeutic use; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3; D000068800:Etanercept