Exogenous procalcitonin evokes a pro-inflammatory cytokine response

Inflamm Res. 2011 Feb;60(2):203-7. doi: 10.1007/s00011-010-0255-8. Epub 2010 Oct 17.

Abstract

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.

MeSH terms

  • Calcitonin / immunology
  • Calcitonin / pharmacology*
  • Calcitonin Gene-Related Peptide
  • Chemotaxis, Leukocyte
  • Cytokines / immunology*
  • Humans
  • Inflammation / immunology*
  • Interleukin-1beta / immunology
  • Interleukin-6 / immunology
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Protein Precursors / immunology
  • Protein Precursors / pharmacology*
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Sepsis / blood
  • Shock, Septic / blood
  • Shock, Septic / immunology
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • CALCA protein, human
  • Cytokines
  • Interleukin-1beta
  • Interleukin-6
  • Protein Precursors
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Calcitonin
  • Calcitonin Gene-Related Peptide