Procalcitonin and Bacterial Infections in the Human Body

Abstract

Procalcitonin (PCT), a member of the calcitonin (CT) superfamily, is a 116 amino acid, 13 kilodalton precursor protein produced in humans in the parafollicular cells of the thyroid as well as the neuroendocrine cells of the lungs and intestines of healthy individuals. PCT is coded for in the Calc‐I gene, located on chromosome 11. PCT is the precursor to the regulatory protein calcitonin but may have its own, separate role in the human body’s response to bacterial infection. There is a positive correlation between the concentration of PCT in the blood and the severity of a bacterial infection, making PCT an acute phase reactant. Under normal conditions, PCT undergoes proteolytic cleavage in the thyroid and is converted into CT, which then leaves the thyroid and enters the bloodstream; however, under inflammatory conditions, PCT is not cleaved and enters the bloodstream in a three‐section state comprising an amino terminus, immature calcitonin, and calcitonin carboxyl‐terminus peptide. Additionally, under inflammatory conditions, PCT is produced in other locations besides the parafollicular cells of the thyroid and the neuroendocrine cells of the lungs and intestines due to an increase in the expression of the Calc‐I gene. The reason for this increase may be related to potential anti‐inflammatory characteristics of PCT, including an ability to signal a reduction in the production of pro‐inflammatory proteins such as tumor necrosis factor‐alpha and interleukin 1‐beta. Furthermore, PCT in a specific concentration has been shown to reduce the reactivity of lipopolysaccharide (LPS) in gram‐negative bacteria. These properties of PCT have many potential applications in the medical field that are currently being studied or used. For example, detection of PCT in the blood can be used to determine if an infection is viral or bacterial or to evaluate the severity of infection in patients with sepsis. The determination of the pathogen allows for the correct course of appropriate treatment, potentially preventing the overprescription and overuse of antibiotics, a critical concern with the continued rise of bacterial antibiotic resistance. Additionally, as patients recover from a systemic bacterial infection, monitoring the level of PCT allows physicians to determine when the course of antibiotics may be stopped, once again minimizing antibiotic overuse. The Walton High School SMART Team has designed a 3D model of procalcitonin to investigate the relationship between procalcitonin’s structure and its function.Support or Funding InformationMSOE Center for Biomolecular Modeling