procalcitonin procalcitonin procalcitonin (pct) is a peptide precursor of the hormone calcitonin, the latter being involved with calcium homeostasis. it arises once preprocalcitonin is cleaved by endopeptidase. it was first identified by leonard j. deftos and bernard a. roos in the 1970s. it is composed of 116 amino acids and is produced by parafollicular cells (c cells) of the thyroid and by the neuroendocrine cells of the lung and the intestine. figure 1: immature calcitonina 3d cartoon of procalcitonin's daughter compound, calcitonin the level of procalcitonin in the blood stream of healthy individuals is below the limit of detection (0.01 µg/l) of clinical assays. the level of procalcitonin rises in a response to a pro-inflammatory stimulus, especially of bacterial origin. it is therefore often classed as an acute phase reactant. the induction period for procalcitonin ranges from 4–12 hours with a half-life spanning anywhere from 22–35 hours. it does not rise significantly with viral or non-infectious inflammations. in the case of virus infections this is due to the fact that one of the cellular responses to a viral infection is to produce interferon gamma, which also inhibits the initial formation of procalcitonin. with the inflammatory cascade and systemic response that a severe infection brings, the blood levels of procalcitonin may rise multiple orders of magnitude with higher values correlating with more severe disease. however, the high procalcitonin levels produced during infections are not followed by a parallel increase in calcitonin or a decrease in serum calcium levels. biochemistry figure 2: production pathway of pct and ct in healthy and infected individuals via the induction of calc-1 genepct is a member of the calcitonin (ct) superfamily of peptides. it is a peptide of 116 amino acid with an approximate molecular weight of 14.5 kda, and its structure can be divided into three sections (see figure 1): amino terminus (represented by the ball and stick model in figure 1), immature calcitonin (shown in figure 1 from pdb as the crystal structure of procalcitonin is not yet available), and calcitonin carboxyl-terminus peptide 1. under normal physiological conditions, active ct is produced and secreted in the c-cells of the thyroid gland after proteolytic cleavage of pct, meaning, in a healthy individual, that pct levels in circulation are very low (<.05 ng/ml). the pathway for production of pct under normal and inflammatory conditions are shown in figure 2. during inflammation, lps, microbial toxin, and inflammatory mediators, such as il-6 or tnf-α, induce the calc-1 gene in adipocytes, but pct never gets cleaved to produce ct. in a healthy individual, pct in endocrine cells is produced by calc-1 by elevated calcium levels, glucocorticoids, cgrp, glucagon, or gastrin, and is cleaved to form ct, which is released to the blood. pct is located on the calc-1 gene on chromosome 11. bacterial infections induce a universal increase in the calc-1 gene expression and a release of pct (>1 μg/ml). expression of this hormone occurs in a site specific manner. in healthy and non-infected individuals, transcription of pct only occurs in neuroendocrine tissue, except for the c cells in the thyroid. the formed pct then undergoes post-translational modifications, resulting in the production small peptides and mature ct by removal of the c-terminal glycine from the immature ct by peptidylglycine α-amidating monooxygenase (pam). in a microbial infected individual, non-neuroendocrine tissue also secretes pct by expression of calc-1. a microbial infection induces a substantial increase in the expression of calc-1, leading to the production of pct in all differentiated cell types. the function of pct synthesized in nonneuroendocrine tissue due to a microbial infection is currently unknown, but, its detection aids in the differentiation of inflammatory processes. diagnostic advantages due to pct’s variance between microbial infections and healthy individuals, it has become a marker to improve identification of bacterial infection and guide antibiotic therapy. the table below is a summary from schuetz, albrich, and mueller, summarizing the current data of selected, relevant studies investigating pct in different types of infections. legend: ✓ = moderate evidence in favor of pct ✓✓ = good evidence in favor of pct ✓✓✓ = strong evidence in favor of pct ~ = evidence in favor or against the use of pct, or still undefined infection type/setting study design pct cut-off (ug/l) pct benefit conclusion