Exogenous procalcitonin evokes a pro-inflammatory cytokine response.

OBJECTIVE AND

DESIGN

Procalcitonin (ProCT) is increased in serum of septic patients and those with systemic inflammation. Endogenous levels of ProCT might influence the response of polymorphonuclear leukocytes (PMNs), independently of endotoxin, in clinical disease.

SUBJECTS: Healthy human volunteers.

TREATMENT: Recombinant human ProCT (rhProCT).

METHODS

Whole blood and PMNs were exposed in vitro to exogenous rhProCT. Interleukin (IL)-6, IL-8, IL-10, IL-13, tumor necrosis factor-alpha (TNFα), IL-1β, and macrophage inflammatory protein (MIP)-1β (pg/ml) were measured by multiplex suspension bead-array immunoassay, and migration and phagocytosis were measured in PMNs.

RESULTS

In a whole-blood model, a dose-dependent increase in IL-6, TNFα, and IL-1β of the cell-free supernatant was noted. Pre-incubation with ProCT, at doses consistent with clinical sepsis, resulted in a decrease in PMN migration without alteration in phagocytosis of Staphylococcus aureus or indirect measurements of bacterial killing.

CONCLUSION

Clinically relevant levels of ProCT influence immunologic responses that may contribute to systemic inflammatory response and septic shock.