Procalcitonin and acute coronary syndromes: a new biomarker for an old disease

Abstract

Procalcitonin (PCT) is a pro-peptide produced in C-cells by the thyroid gland under normal physiological condition. In some clinical conditions of stress, as in sepsis and septic shock, the PCT level is elevated, and its levels are correlated to the severity of the infection; therefore, it has been proposed as a specific marker of sepsis [1]. However, the PCT level also increases moderately in other clinical settings such as trauma, major cardiac surgery, pancreatitis, and cardiogenic shock, showing that it is not a specific marker for sepsis. PCT, although not a specific component of the inflammatory cascade, is released, as most cytokines, under stimulation by bacteria and bacterial components as lipo-polysaccharide (LPS), but its relations with inflammation are complex. Despite much evidence that has shown that PCT levels increase in infectious diseases, the biological mechanisms leading to its production remain unknown. Some authors report that PCT is produced by liver and peripheral blood mononuclear cells (PBMCs) [2]. They also state that there is a correlation between cytokines (like IL-1, IL-6, TNF-a), LPS and PCT, suggesting that the increased levels of cytokines during infection may induce the production of extra-thyroid PCT. In vitro and clinical studies, however, have shown that LPS is the strongest inducer of PCT release [2, 3]. Moreover, clinical studies show that, in comparison with sterile pancreatitis, patients with infected pancreatitis, have significantly increased levels of PCT, whereas IL-8 levels are not modified [4]. Taken all together, these findings suggest that an increase in PCT levels is more pronounced in infections than in non-infectious systemic inflammatory responses, and this phenomenon is related to a great amount of released LPS. As a marker of sepsis, PCT has been compared with C-reactive protein (CRP), with conflicting results [5, 6]. The ambiguous conclusions regarding the diagnostic accuracy of CRP and PCT may be due to different cutoff values and heterogeneous populations. In particular there is not a standardized cutoff value, but various studies suggest that the range for the diagnosis of sepsis is between 0.6 and 5 ng/mL, which is quite large. However, either CRP or PCT is released in sepsis and in non-infectious inflammatory disease, and they are effective but not perfect in distinguishing infection from non-infectious inflammatory disease.