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.