Physiology and genetics of procalcitonin

Procalcitonin (PCT), a protein of 116 amino-acids with molecular weight of 13 kDa, was discovered 25 years ago as a prohormone of calcitonin produced by C-cells of the thyroid gland and intracellularly cleaved by proteolytic enzymes into the active hormone. Circulating levels of PCT in healthy subjects are below detection limit. Since 1993 when its elevated level was found in patients with bacterial infection, PCT became an important protein in the detection and differential diagnostics of inflammatory states. The production of PCT during inflammation is linked with a bacterial endotoxin and with inflammatory cytokines (TNF, IL-6). PCT detectable in the plasma during inflammation is not produced in C-cells of the thyroid. The probable site of PCT production during inflammation are the neuroendocrine cells in the lungs or intestine. There is no evidence of plasma PCT binding to cellular receptors of calcitonin, and the role of PCT in calcium and phosphate metabolism during sepsis is still not clear. Other hypothetical roles of PCT (cytokine network regulation, PCT as an endogenous non-steroid antiinflammatory drug) are being considered.