Tumor necrosis factor induces adult respiratory distress syndrome in rats

To evaluate the effect of tumor necrosis factor (TNF), a major mediator of sepsis, on lung structure and function, we infused 200-g male Wistar rats with TNF (0, 2 x 10(5), or 4 x 10(5) U/kg of TNF) for 24 hours. Volume-pressure measurements were determined in the excised lungs using both air and saline, which eliminated surface tension forces. Total lung wet and dry weight, nitrogen level, and DNA and protein content were measured. Lungs of the rats that received TNF accepted significantly smaller volumes of air and saline at all pressures compared with the control group. Both the lung wet and dry weights increased with TNF. Lung DNA and protein content also increased, suggesting increased cellularity in the TNF-infused lungs. Thus, the lungs of the TNF-treated rats were stiffer, with reduced compliance values, and heavier due to increased water content and increased cellularity. These data indicate that sublethal administration of TNF in this rat model induces the adult respiratory distress syndrome and increases the work potential of respiration.