Effect of pentoxifylline on survival and intestinal cytokine messenger RNAtranscription in a rat model of ongoing peritoneal sepsis

Objective: Septic animals receiving high-protein liquid diets have increase d mortality and increased production of cytokines by the gut compared with animals receiving low-protein diets. The purpose of this study was to evalu ate the ability of pentoxifylline to alter gut cytokine production in a rat model of prolonged acute peritonitis, to determine its effect on survival in such animals, and to determine whether alteration of gut cytokine produc tion was associated with survival, Design: Prospective, randomized animal study, Setting: Research laboratory. Subjects: Male Lewis rats weighing between 250 and 300 g. Interventions: Anesthetized rats had placement of a gastrostomy, followed I wk later by implantation of a bacteria filled osmotic minipump into the pe ritoneal cavity, Rats were fed a high protein (20% total energy) enteral di et, Saline or pentoxifylline (5 or 20 mg/kg im) was administered daily begi nning at the time of pump implantation. Measurements and Main Results: Septic rats fed the high protein liquid diet and given pentoxifylline in a dose of 5 mg/kg/day demonstrated improved su rvival compared with saline treated animals or animals given the high dose (20 mg/kg/day) of pentoxifylline (p <.05), Administration of pentoxifylline at 5 mg/kg/day also down regulated the production of IL-6 messenger RNA (m RNA) in liver and lipopolysaccharide binding protein mRNA in the liver and intestine of septic animals given the high-protein liquid diet, Conclusion: Low-dose (but not high-dose) pentoxifylline administration redu ced production of some, but not all, cytokines studied in the gut and liver in a rat model of acute peritonitis and this reduced production was associ ated with an improved survival in such animals.