PCT - Molecule & Kinetics

Molecule and stability

Procalcitonin (PCT) is a 116 amino acid protein with a sequence identical to that of the prohormone of calcitonin (32 amino acids). Under normal metabolic conditions, hormonally active calcitonin is produced and secreted in the C-cells of the thyroid gland after specific intracellular proteolytic procession of the prohormone PCT. Thus, under normal conditions the PCT levels in the circulation are very low (< 0.05 ng/ml).

Bacterial infections induce an ubiqitous increase of CALC-1 gene expression and a constitutive release of PCT from all parenchymal tissues and differentiated cell types throughout the body, so that significant concentrations of PCT (up to 1000 ng/ml) can be detected in the blood of patients with severe bacterial infection/sepsis.

The PCT molecule is very stable both in vivo and in vitro. Therefore no special requirements to pre-analytical sample handling and storage are required. The in vivo half-life time of PCT is about 24 hours.

PCT sepsis

 

PCT Induction in Sepsis:
Calcitonin- and Cytokine mRNA Expression in Sepsis versus Controls

Quantitative Analysis of CT-mRNA Expression by Taq-Man PCR technology shows a significant induction in all septic tissues. Parenchymal cells (including liver, lung, kidney, adipocytes and muscle) provide the largest tissue mass and principal source of circulating PCT in sepsis. Compared to classical cytokines, the transcriptional expression of Calcitonin-mRNA seemed more uniformely up-regulated in sepsis1. The inflammatory release of PCT can be induced either directly via microbial toxines (eg, endotoxin) or indirectly via a humoural or cell-mediated host response (eg, IL-1ß, TNF-alpha, IL-6). The induction can be attenuated by cytokines also released during a viral infection (eg, interferon-gamma). In sepsis, the predominance of PCT as opposed to mature CT is indicative of a constitutive pathway within cells lacking secretion granules, and, hence, a bypassing of much of the enzymatic processing.2


PCT Kinetics

Procalcitonin (PCT) increases after 2-3 hours after induction e.g. by endotoxin and may increase to levels up to several hundred nanogram per ml in severe sepsis and septic shock. After successful treatment intervention the procalcitonin value decreases, indicating a positive prognosis. Persistingly high or even further increasing levels are indicators for poor prognosis.
After induction, e.g. by endotoxin, PCT increase is observed within 2-3 hours. Levels then rise rapidly, reaching a plateau after 6-12 hours. PCT concentrations remain high for up to 48 hours, falling to their baseline values within the following 2 days. The half-life is about 20 to 24 hours3.

PCT sepsisFigure: PCT plasma concentrations (ng/ml) following infusion of an accidentally bacterially (Acinetobacter baumanii) contaminated infusion solution to a 76 year-old female patient. The induction period can be described according to 2 types of kinetics: during the first phase (<6h), PCT increased by approximately 0.5 ng/ml per hour after a latency phase of about 2-3 hours (first measurable value recorded at time = 3h) followed by massive PCT production at the rate of approximately 50 ng/ml per hour over subsequent hours.4

 

References:

  1. Beat Müller et al., J Clin Endocrinol Metabol, 2000, 86: 396-404
  2. Linscheid P. et al. Endocrinology 2003, 144:5578-5584
  3. Meisner M., Procalcitonin - Biochemistry and Clinical Diagnosis, © UNI-MED Science, 1st edition 2010, ISBN 978-3-8374-1241-3 (Germany) / ISBN 978-1-84815-163-5 (Rest of the world)
  4. Brunkhorst F.M. et al., Intens Care Med 1998, 24: 888-892

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