ACUTE BACTERIAL PNEUMONIA IN RATS INCREASES ALVEOLAR EPITHELIAL FLUIDCLEARANCE BY A TUMOR NECROSIS FACTOR-ALPHA-DEPENDENT MECHANISM

To study the rate and regulation of alveolar fluid clearance in acute pneumonia, we created a model of Pseudomonas aeruginosa pneumonia in r ats. To measure alveolar liquid and protein clearance, we instilled in to the airspaces a 5% bovine albumin solution with 1.5 mu Ci of I-125- human albumin, 24 h after intratracheal instillation of bacteria. The concentration of unlabeled and labeled protein in the distal airspaces over 1 h was used as an index of net alveolar fluid clearance. Since there was histologic evidence of alveolar epithelial injury, several m ethods were used to measure alveolar fluid clearance, including the us e of experiments in rats with blood flow and the use of experiments in rats without blood flow, so that movement across the epithelial barri er would be minimized in the latter group. The results with each metho d were identical. We found that P. aeruginosa pneumonia increased alve olar liquid clearance over 1 h by 48% in studies with blood flow, and by 43% in rats without blood flow, compared with respective controls ( P < 0.05). In both studies, this increase was inhibited with amiloride . However, propranolol had no inhibitory effect, thus ruling out a cat echolamine-dependent mechanism to explain the increase in alveolar flu id clearance, An antitumor necrosis factor-alpha neutralizing antibody , instilled into the lung 5 min before bacteria, prevented the increas e in alveolar liquid clearance in rats with pneumonia (P < 0.05). Also , TNF alpha (5 mu g) instilled in normal rats increased alveolar liqui d clearance by 43% over 1 h compared with control rats (P < 0.05). In normal rats instilled with TNF alpha, propranolol had no inhibitory ef fect. In conclusion, gram-negative pneumonia markedly upregulates net alveolar epithelial fluid clearance, in part by a TNF alpha-dependent mechanism. This finding provides a novel mechanism for the upregulatio n of alveolar epithelial sodium and fluid transport from the distal ai rspaces of the lung.