Injurious mechanical ventilation increases BALF levels of both sTNFR p55 and p75. Mice were ventilated with low tidal volume [VT; 8–9 ml/kg, with the initial peak inspiratory pressure (PIP) set at ∼10 cmH2O] or high-VT (36–41 ml/kg, with the initial PIP set at ∼35 cmH2O) ventilation for up to 2 h. On termination, BALF was analyzed for sTNFRs, MIP-2, and total protein. A: high-VT ventilation produced small marginal increases in BALF total protein at 0.5 and 1 h, followed by a large increase at 2 h, indicating progressive increases in alveolar epithelial permeability. B: high-VT ventilation also produced a significant increase in BALF MIP-2 at 2 h, although levels were considerably lower than for intratracheal LPS (Fig. 1B). C: high-VT ventilation substantially increased BALF sTNFR p55 levels at 2 h. D: high-VT ventilation for 1 h produced a small increase in BALF sTNFR p75 levels, with a larger increase at 2 h. Note that increased sTNFR levels were not apparent before the substantial increase in BALF total protein. Dashed lines indicate baseline values from untreated mice. *P < 0.05, high VT vs. low VT; n = 5–7/each group.