Objective: To observe the effect of 5-fluorouracil (5-FU) on modulation of the disorders of proinflammatory and anti-inflammatory cytokines in the severe sepsis as a result of intra-abdominal infection in rat, and to investigate the mechanism of efficacy of 5-FU in the treatment of severe sepsis.
Methods: Thirty female Wistar rats were randomly divided into three groups: control group, severe sepsis group and 5-FU group. Healthy rats served as control (n=10). Severe sepsis was induced by peritoneal injection of 1.8x10(12) cfu/L E. coli with the volume of 10 ml/kg body weight. In the 5-FU group, 50 mg/kg of 5-FU was injected intraperitoneally 40 minutes after severe sepsis was induced. All rats were sacrificed 6 hours after operation. The mortality and the ascites rate were assessed 6 hours after sepsis. At the same time the wet weight of the lung was measured and venous blood was collected for determination of concentrations of interleukin-6 (IL-6) and IL-10.
Results: Compared with those of severe sepsis group, the mortality and the ascites rate at 6 hours were decreased significantly in 5-FU group (P<0.05 and P<0.01). The wet weight of lung in severe sepsis group was higher significantly than that in control group (P<0.01). The lung tissue wet weight in 5-FU group was lower than that of severe sepsis group (P<0.05), but it showed no difference when compared with that of control group. The levels of IL-6 and IL-10 in severe sepsis group were higher significantly than those in control group (both P<0.01). The level of IL-6 in 5-FU group was lower than that in severe sepsis group, but with no difference compared with that of control group. The level of IL-10 in 5-FU group was also lower than that in severe sepsis group, but higher than that in control group (both P<0.01).
Conclusion: 5-FU may lower simultaneously the level of proinflammatory IL-6 and anti-inflammatory IL-10, alleviate lung edema and inflammation. 5-FU has the protective effect against severe sepsis in rat.