Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro

Procalcitonin (PCT), the precursor of calcitonin, was recently put forward as a diagnostic marker of systemic bacterial infection and sepsis. The majo r PCT production site in sepsis still remains unclear, Because of a certain association between increased levels of PCT and leukocyte-derived cytokine s during sepsis, we assessed the possible expression of PCT in human periph eral blood mononuclear cells (PBMCs) and the modulation of PCT by lipopolys accharides (LPS) and various sepsis-related cytokines by reverse transcript ase-polymerase chain reaction (RT-PCR) by using a novel primer set and flow cytometric analysis with intracellular staining with antibodies to the PCT components calcitonin and katacalcin. RT-PCR and flow cytometric analysis demonstrated that PBMCs express PCT both on mRNA and on protein levels. LPS and various proinflammatory cytokines (interleukin-1 beta (IL-1 beta), IL- 6, tumor necrosis factor-alpha (TNF-alpha), IL-2) had pronounced stimulator y effects on the expression of PCT mRNA. Under identical experimental condi tions the anti-inflammatory cytokine IL-10 had no effect on the expression of mRNA for PCT, Flow cytometric analysis demonstrated increased intracellu lar amounts of PCT components after LPS stimulation, Thus we demonstrate fo r the first time that PCT is expressed in PBMCs, This expression is modulat ed by bacterial LPS and sepsis-related cytokines. Therefore PBMCs may be am ong the sources of elevated PCT levels in patients with sepsis.