PENTOXIFYLLINE IMPROVES SURVIVAL AND REDUCES TUMOR-NECROSIS-FACTOR, INTERLEUKIN-6, AND ENDOTHELIN-1 IN FULMINANT INTRAABDOMINAL SEPSIS IN RATS

The influence of pentoxifylline (PTX) on mortality and some important mediators was studied in a model of cecal perforation with fulminant i ntra-abdominal sepsis in rats. Cumulative mortality was registered in three groups of animals: untreated sepsis (n = 36), sepsis + PTX 20 mg /kg/24 h (n = 24), and sepsis + PTX 80 mg/kg/24 h (n = 24). PTX therap y was started at sepsis induction or after 4 h, and mortality was redu ced from 89% in untreated sepsis to 60-66% in the PTX groups. Levels o f sepsis mediators were studied in two groups: untreated sepsis and se psis + PTX 40 mg/kg started 1 h after sepsis induction. In both groups 6-10 animals were sacrificed at 4 and 8 h to measure blood levels of bacteria, endotoxin, tumor necrosis factor (TNF), interleukin-6 (IL-6) , endothelin-1, lactate, neutrophils, and packed cell volume. Cecal pe rforation gave high levels of bacteria, endotoxin, TNF, IL-6, and endo thelin-1, leading to dehydration, lactacidosis, neutropenia, and death . Treatment with PTX did not modify dehydration, neutropenia, or conce ntrations of bacteria and endotoxin. Release of endothelin-1 was delay ed, TNF burst was nearly abolished, and levels of IL-6 and lactate wer e substantially suppressed. In summary, PTX improves survival and redu ces blood concentrations of TNF, IL-6, lactate, and endothelin-1 in fu lminant intra-abdominal sepsis in rats. The primary effect of PTX in t his sequence is probably reduction of TNF.