The search for sensitive and specific markers of systemic infection has shown that procalcitonin levels are increased in sepsis, and, consequently, this plasma protein has come into the focus of clinical research. Human procalcitonin is encoded by theCalc-Igene, which gives rise to two alternatively spliced transcripts. Despite systemic investigation of theCalc-Igene and mechanisms of the tissue-specific regulation and alternative splicing, little is known about the biology of procalcitonin and the cells which express this protein during inflammation. Here we focus on the molecular and biochemical properties of the molecule and summarize the known biological functions of procalcitonin. We report on the structure of theCalc-Igene, the amino acid conservation of procalcitonin in different species, and the consensus sequences of the protein with regard to sites relevant for posttranslational modification, spatial distribution, and homologies to other cytokines. We discuss aspects of intracellular location of procalcitonin and demonstrate that it has the characteristics of a secreted protein.

Procalcitonin (PCT) is a highly sensitive and specific marker of systemic bacterial infection and sepsis. In contrast to its diagnostic significance, the cellular sources of plasma procalcitonin remain to be clarified. Two forms of PCT mRNAs originate from calcitonin/calcitonin gene-related peptide gene (CALC-I gene) along with mRNA for calcitonin gene-related peptide-I (CGRP-I). Reverse transcription polymerase chain reaction with newly designed primers detecting different PCT mRNAs and CGRP-I mRNA was used to identify tissues that might contribute to PCT production. Our study indicates that a variety of human tissues (13 of the 16 analyzed overall) express PCT-I, PCT-II, and/or CGRP-I mRNAs, with the highest levels detected for liver, testis, lung, prostate, kidney, and small intestine. Various tissues differ in the proportions of PCT-I, PCT-II, and CGRP-I mRNA expression levels. Thus we demonstrate the complexity of tissue-specific regulation of CALC-I gene expression and suppose a variety of tissues as a potential source of CALC-I-encoded peptides.

Hypothermia is associated with elevated frequency of infectious complications. Dysfunction of the immune response caused by hypothermia has been demonstrated in both clinical and animal studies, but it still remains unclear to what extent immunocompetent cells are directly influenced by hypothermia. To estimate the direct influence of mild hypothermia on cytokine expression and release by human peripheral blood mononuclear cells (PBMC), primary cultures of PBMC were incubated at 34°C or 32°C activated by lipopolysaccharide (LPS), phytohemagglutinin (PHA), or tumor necrosis factor-α (TNF-α). The cytokine gene expression was evaluated by RT-PCR. Release of interleukin-2 (IL-2), IL-6, IL-10, and TNF-α was measured by ELISA. Mild hyperthermia significantly impaired IL-2 gene expression in PHA-stimulated cultures of PBMC and decreased IL-2 release in all variants of cultures. Secretion of IL-6, IL-10, and TNF-α was decreased in hypothermic cultures of PBMC stimulated with the T lymphocyte activator PHA. Slight suppression of IL-10 secretion was observed also in TNF-α-stimulated hypothermic cultures of PBMC. TNF-α release increased slightly in mild hypothermia control cultures. Our data demonstrate that the direct influence of hypothermia on cytokine expression and release from PBMC is not uniform. Reduction of IL-2 production might play a crucial role in the impairment of immune response in hypothermia.