Exogenous procalcitonin evokes a pro-inflammatory cytokine response.
OBJECTIVE
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.


METHODS
Healthy human volunteers.


METHODS
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.


CONCLUSIONS
Clinically relevant levels of ProCT influence immunologic responses that may contribute to systemic inflammatory response and septic shock.
Medical Service and Section of Infectious Diseases, Veterans Affairs Medical Center, 50 Irving Street, NW 4A155, Washington, DC, USA. angelike.liappis@va.gov
Angelike P
AP
Liappis
Kevin W
KW
Gibbs
Eric S
ES
Nylen
Bona
B
Yoon
Richard H
RH
Snider
Baochong
B
Gao
Kenneth L
KL
Becker
D002116:Calcitonin / Q000276:immunology / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D011498:Protein Precursors / Q000276:immunology / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D018805:Sepsis / Q000097:blood; D012772:Shock, Septic / Q000097:blood / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
C000606589:CALCA protein, human; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D011498:Protein Precursors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide