Procalcitonin m-RNA is expressed by human mononuclear cells and modulated by lipopolysaccharide and sepsis related cytokines

Introduction: Procalcitonin (PCT), the precursor of calcitonin, is produced under physiological conditions in the thyroid. It was recently identified as a marker of severe especially bacterial infection. Elevated PCT levels have been demonstrated in septic patients also after thyroidektomy. Therefore other sites of PCT expression have to be considered. Methods: Possible PCT mRNA expression in peripheral blood mononuclear cells (MNC) from healthy humans was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) using a novel primer set (B.R.A.H.M.S, Berlin). Levels of PCT mRNA expression were estimated in control and cultures of MNC stimulated by lipopolysaccharides (LPS) and sepsis related cytokines. Restriction mapping was performed to verify the specificity of PCR primers for human PCT by digestion of PCR amplified thyroid medullary carcinoma cDNA. Results: RT-PCR analysis demonstrated that MNC express mRNA for PCT and that LPS as well as various cytokines may modulate this expression. In the cultures stimulated with LPS from E. coli B4 and Salmonella abortus equi the final RT-PCR product for PCT mRNA was elevated up to 200% to 2300% in comparrison with 100% in control culture. Pronounced effects were also observed for IL-1β - 100-1800%; IL-6 - 200-3500%; TNF-α - 200-9000%; IL-2 - 250-1500%. IL-10 had no effect on the expression of mRNA for PCT. Conclusions: We demonstrate for the first time that PCT is expressed in MNC. This expression is modulated by bacterial LPS and sepsis related cytokines. Therefore MNC may be one of the sources for elevated plasma PCT levels in septic patients.