The effect of tumor necrosis factor-α on microvascular permeability in an isolated, perfused lung

This study examines the hypotheses that TNF-α causes a dose-dependent increase in the microvascular permeability of ex vivo buffer perfused lungs that is quantitatively similar to that caused by lipopolysaccharide (LPS) or thromboxane A₂ (TxA₂). We also postulated that TNF-α potentiates the effect of interleukin-1β (IL-1β) or TxA₂ receptor activation on pulmonary microvascular permeability. Lungs harvested from Wistar rats were perfused ex vivo with Krebs-Henseleit buffer containing 0, 10, 100, or 1000 ng/mL recombinant rat TNF-α. Twenty minutes later pulmonary microvascular permeability was determined by measuring the capillary filtration coefficient (K_f) using a gravimetric technique. The effect of TNF-α (100 ng/mL) on pulmonary K_f was compared with that of lungs exposed to LPS (400 μg/mL; E. coli 0111:B4) or a TxA₂ receptor agonist (U-46619; 7 × 10^-8). In other experiments, perfused lungs were exposed to TNF-α plus IL-1β (1 ng/mL) or TNF-α plus U-46619 after which K_f was measured. Exposure of ex vivo buffer perfused lungs to 10 - 1000 ng/mL TNF-α had no effect on K_f whereas LPS and U-46619 was associated with a two- and six-fold increase in K, respectively (P < 0.05). The K_f of lungs exposed to TNF-α plus IL-1 was similar to that of lungs exposed to TNF-α alone. Lastly, the K_f of lungs exposed to TNF-α plus U-46619 was not different than that of lungs exposed to U-46619 alone. In conclusion, TNF-α at least when administered for a relatively brief period of time does not affect microvascular permeability in an isolated, buffer-perfused lung model.