Anti-inflammatory effect of procalcitonin on in vitro LPS-stimulated human PBMC

Introduction

Sepsis is a leading cause of death in critically ill patients and is characterized by a marked increase of the host proinflammatory cytokine release that is precipitated by infectious agents. The sepsis response to therapy has not appreciably improved. The procalcitonin (PCT) concentration is increased in the serum samples of septic patients and correlates with severity of the illness. LPS is a pivotal bacterial product involved in pathogenesis of sepsis and septic shock. Preventing the beginning of inflammatory systemic cascade by means of LPS modulating agents might have a valuable effect in the control of such deadly illness. The aim of the present study was to evaluate the potential effect of procalcitonin on in vitro LPS-induced release of cytokines from human PBMC.

Methods

S. typhimuriumLPS was preincubated with human PCT and then was added to freshly isolated human PBMC cultures in RPMI 1640. In such cultures the final concentrations of LPS and PCT were 10 ng/ml and either 5,000 or 500 ng/ml respectively. A panel of cytokines was evaluated on culture supernatants by Biochip microarray (Randox) and PCT was tested by ELFA. Data analysis was carried out by a nonparametric method (Mann-Whitney U test, Graph Pad Prism version 4.03) to establish statistical differences between groups.

Results

Both of the PCT concentrations used significantly (P < 0.05 vs. LPS-stimulated PCT-free controls) reduced TNFα (after 4-hour incubation with LPS) and MCP-1 (24 hours following LPS challenge). The lower concentration of PCT was also able to significantly (P < 0.05 vs. LPS-stimulated PCT-free controls) decrease the TNFα and IL-2 levels in the 24-hour samples.

Conclusions

PCT, besides the well-known role as marker of sepsis, could be a potentially useful molecule to control systemic inflammatory mediators in both sepsis and septic shock.