Procalcitonin's role in the sepsis cascade. Is procalcitonin a sepsis marker or mediator?

PCT is a 116-amino acid polypeptide glycoprotein that is ubiquitously expressed from various extrathyroid neuroendocrine tissues during bacterial infection. PCT was shown to closely correlate with the severity of sepsis. PCT synthesis is probably induced by tumor necrosis factor-alpha (TNFalpha) or interleukin-6 (IL-6), the primary cytokines in the inflammatory cascade, as they always peak before PCT. In healthy and septic animals, PCT injection did not initiate or enhance the production of TNFalpha, while TNFalpha injection induced a 25-fold massive and sustained PCT increase. This indicates that PCT release is not a ''proximal'' but rather an ''intermediary'' event in the sepsis cascade that requires a ''primed'' inflammatory background to exert its effect. PCT, a prohormone that follows a cytokine-like expression pathway, was coined a ''hormokine'' to signify its cytokine-like host-response. In our center, over a period of 2 years, we investigated subsets of postoperative ICU patients with sepsis. The area under the Receiver Operating Characteristic curve for PCT's prediction of survival outcome demonstrated a very high discriminative power of 0.90 from day 6, with a cut-off value of 3.2 ng mL(-1) PCT concentration. Interestingly, in our study, PCT declined a few days before a lethal outcome. This ominous sign clearly demonstrates that patients with poor prognosis would manifest, at a certain stage, a decrease in their ability to mount an effective response to sepsis.