Overview of procalcitonin in pregnancy and in pre‐eclampsia

Summary Procalcitonin (PCT), a precursor for calcitonin, is a prohormone involved in the inflammatory processes, which has been poorly studied in the context of pregnancy. During severe inflammation, PCT derives from almost all cell types, including monocytes and parenchymal tissues, making it a good predictive and diagnostic marker of an inflammatory state with rapidly increased serum levels in inflammation or sepsis. In normal pregnancy, PCT is basally expressed at very low level by decidual cells, even if decidual macrophages, which in normal pregnancy are skewed to M2 macrophages, are resistant to lipopolysaccharide (LPS)‐induced production of PCT. As PCT increase is associated with an inflammatory state, several research groups investigated whether PCT can be considered a marker of pre‐eclampsia, a pregnancy disease characterized by systemic inflammation. The first aim of this review is to summarize what is already known about the tissues synthesizing PCT, about the stimuli that cause the increase of circulating PCT levels and how PCT acts as a proinflammatory stimulus by itself. Secondly, we will describe the role of this prohormone in normal pregnancy and in pregnancies complicated by pre‐eclampsia, highlighting the involvement of the decidual macrophages and the proinflammatory cytokine tumor necrosis factor‐α in the modulation of PCT expression in the decidual microenvironment. ‐PCT, the pro‐hormone of calcitonin, is produced from almost all cell types mainly by two alternative mechanisms: direct pathway induced by bacterial endotoxins or other toxic metabolites from microbes, and indirect pathway stimulated by various proinflammatory cytokines such as tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6 and IL‐8. ‐During pre‐eclampsia (PE) the increase of circulating pro‐inflammatory cytokines induces an augmentation of PCT. ‐PCT serum levels can be considered a good diagnostic marker of PE, although it cannot be considered a predictive marker of PE onset. ‐PCT emerges as a good prognostic marker of the severity of PE.