Mechanisms of Pulmonary Edema Induced by Tumor Necrosis Factor-a

We tested the hypothesis that human recombinant tumor necrosis factor-a (TNF) promotes pulmonary edema by neutrophil-dependent effects on the pulmonary vasculature. The isolated guinea pig lung was perfused with phosphate-buffered Ringer's solution with or without human neutrophils. The infusion of neutrophils (9x 106 total) into lungs isolated after the in vivo administration of TNF (3.2x 10' units/kg) resulted in weight gain (+1.951±0.311 g versus -0.053 0.053 g in control) and an increase in the lung (wet-dry)-to-dry weight ratio (8.3±0.5 versus 6.0±0.2 in control), indicating the formation of pulmonary edema. The neutrophildependent pulmonary edema induced by TNF was associated with a combination of increased capillary permeability (capillary filtration coefficient [KJ,si 0.170+0.048 g/min/cm H20/g at 30 minutes versus 0.118±0.008 g/min/cm H20/g at baseline) and increased pulmonary capillary