Jl. Nelson et al., Effect of pentoxifylline on survival and intestinal cytokine messenger RNAtranscription in a rat model of ongoing peritoneal sepsis, CRIT CARE M, 27(1), 1999, pp. 113-119
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.