Objective: To correlate the dynamics of peritoneal cytokines with systemic concentrations and survival outcome.
Design: Randomized, controlled study using a recently developed rat model of peritonitis.
Setting: Government research facility.
Subjects: Male Sprague-Dawley rats.
Interventions: Infected animals (INF) received an intraperitoneal infusion of 6.5 x 10(8) colony-forming units of Escherichia coli over 12 hrs, whereas control rats (CON) received a sterile inoculum. Peritoneal fluid and plasma samples were obtained from all rats at the end of the 12-hr infusion period as well as from all animals that survived the 7-day study (SURV).
Measurements and main results: Interleukin (IL)-1beta concentration in the peritoneal fluid at 12 hrs tended to be higher in nonsurvivors (NONSURV) than in SURV. Tumor necrosis factor-alpha and IL-6 peritoneal concentrations at 12 hrs were significantly greater in NONSURV than in SURV. There were no significant differences in IL-2 and IL-4 peritoneal concentrations at 12 hrs between SURV and NONSURV. Although the concentrations of IL-1beta and tumor necrosis factor-alpha in the peritoneal fluid of INF decreased gradually during the study, these concentrations remained significantly higher than those of CON at 7 days. In contrast, peritoneal IL-2 concentrations remained lower in INF than in CON for most of the experiment. Peritoneal IL-6 concentrations in INF were transiently elevated above those of CON for 12 hrs. Cytokine concentrations in the peritoneal fluid of INF were always higher than those in plasma, which remained relatively unchanged throughout the study. For most of the variables as. sessed, CON showed no significant changes compared with INF.
Conclusions: This model of peritonitis is associated with a significant and prolonged peritoneal inflammatory response that is adversely correlated with survival outcome. Our data would suggest that to be effective, novel immunotherapies should target mainly the peritoneal compartment.