Pentoxifylline does not improve outcome in a murine model for the multiple-organ dysfunction syndrome

Abstract

Objective: To investigate the effects of pentoxifylline (PTX) administration in a murine model for the multiple-organ dysfunction syndrome (MODS). Design and setting: Prospective double-blind randomized animal study in a university research laboratory. Interventions and measurements: Sixty C57BL/6 mice were given an aseptic intraperitoneal injection of lipopolysaccharide followed after 6 days by zymosan (day 0) at a dose of either 0.9 or 1.0 mg/g body weight. Starting on day 0 mice were administered PTX at a dose of 80 mg/kg body weight or saline per os every 8 h. On day 17 surviving animals were killed, and their liver, lungs, spleen, and kidneys were collected. Results: Mortality, course of body temperature, body weight, and macroscopic lung damage were similar between zymosan-treated groups. Administration of PTX did not significantly alter survival, body temperature, body weight, or macroscopic lung damage. In addition, there were no significant differences in organ weights between mice that received PTX and mice that received PBS. Although PTX inhibited the lipopolysaccharide-induced increase in tumor necrosis factor α and interleukin 6 expression (but not interleukin 1β expression) at both mRNA and protein level in a murine macrophage cell line, tumor necrosis factor α mRNA expression in the livers of PTX-treated mice was not significantly inhibited. Conclusions: The results reported here do not support the hypothesis that PTX improves outcome in zymosan-induced multiple-organ dysfunction in mice. © Springer-Verlag 2005.