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

Crit Care Med. 1999 Jan;27(1):113-9. doi: 10.1097/00003246-199901000-00038.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacteremia / drug therapy*
  • Bacteremia / immunology
  • Bacteremia / mortality
  • Critical Care
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Dietary Proteins / administration & dosage
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Intestines / drug effects*
  • Intestines / immunology
  • Liver / drug effects
  • Liver / immunology
  • Male
  • Pentoxifylline / pharmacology*
  • Pentoxifylline / therapeutic use
  • Peritonitis / drug therapy*
  • Peritonitis / immunology
  • Peritonitis / mortality
  • Phosphodiesterase Inhibitors / pharmacology*
  • Phosphodiesterase Inhibitors / therapeutic use
  • Prospective Studies
  • RNA, Messenger / metabolism*
  • Random Allocation
  • Rats
  • Rats, Inbred Lew
  • Survival Analysis
  • Transcription, Genetic / drug effects

Substances

  • Cytokines
  • Dietary Proteins
  • Phosphodiesterase Inhibitors
  • RNA, Messenger
  • Pentoxifylline