Procalcitonin release patterns in a baboon model of trauma and sepsis: Relationship to cytokines and neopterin

Objectives: Procalcitonin (PCT) has been described as an early, discriminat ing marker of bacteria-associated sepsis in patients. However, little is kn own of its source and actions, in part because no appropriate animal models have been available. We tested the hypothesis that plasma PCT increases du ring various pathophysiological conditions, such as hemorrhagic shock and s epsis, which differ with regard to the degree of associated endotoxemia. We further hypothesized that in sepsis, PCT would be significantly different in survivors vs, nonsurvivors. Design:Prospective, blinded analysis of previously collected plasma of expe rimental animals. Setting: Independent nonprofit research laboratory in a trauma hospital and a contract research institute. Subjects: A total of 22 male baboons (17.5-31 kg). Interventions: Hemorrhagic-traumatic shock was induced by hemorrhage for up to 3 hrs, reperfusion with shed blood and infusion of cobra venom factor ( n = 7). By using a similar experimental setup, severe hyperdynamic sepsis w as induced (n = 15) by intravenous infusion of live Escherichia coil (2 x 1 0(9) colony-forming units/kg) over 2 hrs, followed by antibiotic therapy (g entamicin 4 mg/kg twice a day). Measurements and Main Results: Plasma PCT at baseline was barely detectable , but levels increased significantly (p < .05) to 2 +/- 1.8 pg/mL 2 hrs aft er the start of reperfusion in the shock group, and to 987 +/- 230 pg/mL at 4 hrs after E. coli in the sepsis group. Levels were maximal between 6 and 32 hrs and had returned nearly to baseline levels at 72 hrs. Interleukin-8 levels paralleled the course of PCT measurements, whereas a significant in crease in neopterin was seen at 24 hrs. PCT levels were approximately three times higher in the sepsis group than in the shock group, corresponding to endotoxin levels (at the end of hemorrhage, 286 +/- 144 pg/mL vs. 3576 +/- 979 pg/mL at the end of E. coli infusion; p = .003). PCT levels were signi ficantly different at 24 hrs between survivors (2360 +/- 620 pg/ml) and non sunrivors (4776 +/- 563 pg/ml) in the sepsis group (p = .032), as were inte rleukin-6 (1562 +/- 267 vs. 4903 +/- 608 pg/mL; p = .01) and neopterin/crea tinine ratio (0.400 +/- 0.038 vs. 0.508 a 0.037; p = .032). Conclusions: PCT is detectable in the baboon as in humans, both in hemorrha gic shock and sepsis. PCT levels are significantly higher in sepsis than in hemorrhage, a finding that is probably related to the differences in endot oxin. The baboon can be used for the study of PCT kinetics in both models; PCT kinetics are clearly different from other markers of sepsis, either IL- 6 or neopterin, in both models. There are significant differences between s urvivors and nonsurvivors in the sepsis model.