OBJECTIVE: Septic animals receiving high-protein liquid diets have increased mortality and increased production of cytokines by the gut compared with animals receiving low-protein diets. The purpose of this study was to evaluate 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 production 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 1 wk later by implantation of a bacteria-filled osmotic minipump into the peritoneal cavity. Rats were fed a high-protein (20% total energy) enteral diet. Saline or pentoxifylline (5 or 20 mg/kg im) was administered daily beginning 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 survival 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 (mRNA) 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 reduced 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 associated with an improved survival in such animals.
OBJECTIVE: Septic animals receiving high-protein liquid diets have increased mortality and increased production of cytokines by the gut compared with animals receiving low-protein diets. The purpose of this study was to evaluate 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 production 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 1 wk later by implantation of a bacteria-filled osmotic minipump into the peritoneal cavity. Rats were fed a high-protein (20% total energy) enteral diet. Saline or pentoxifylline (5 or 20 mg/kg im) was administered daily beginning 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 survival 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 (mRNA) 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 reduced 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 associated with an improved survival in such animals.
Authors: Ya-Ching Hsieh; Michael Frink; Bjoern M Thobe; Jun-Te Hsu; Mashkoor A Choudhry; Martin G Schwacha; Kirby I Bland; Irshad H Chaudry Journal: Mol Immunol Date: 2006-12-19 Impact factor: 4.407