title: Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro.
abstract: OBJECTIVE
  Procalcitonin (PCT) is a 13 kD protein of which plasma concentrations are strongly increased in inflammatory states. PCT concentrations are claimed to have a more powerful discriminatory value for bacterial infection than the acute phase proteins serum amyloid A (SAA) or C-reactive protein (CRP). The source of production and its mechanism of induction are unknown. We investigated the inducibility of PCT both in vivo and in vitro and compared the behavior of PCT with those of SAA and CRP.
  
  
  METHODS
  A prospective descriptive patient sample study and a controlled liver tissue culture study.
  
  
  METHODS
  A university hospital.
  
  
  METHODS
  Cancer patients who were treated with human tumor necrosis factor-alpha (rhTNF-alpha; 5 patients) or interleukin-6 (rhIL-6; 7 patients).
  
  
  RESULTS
  Serial serum samples were collected for analysis of concentrations of PCT, SAA, and CRP. In the TNF-alpha group, frequent sampling was performed on the first day to allow analysis of initial responses. In a human liver slice model, the release of PCT, SAA, and CRP was measured on induction with rhTNF-alpha and rhIL-6 for 24 hrs. We found that PCT displayed acute phase reactant behavior in vivo after administration of both rhTNF-alpha and rhIL-6. After rhTNF-alpha-administration, PCT reached half-maximal concentrations within 8 hrs, 12 hrs earlier than either SAA or CRP did. PCT, SAA, and CRP were produced in detectable quantities by liver tissue in vitro. PCT production by liver slices was enhanced after stimulation with rhTNF-alpha or rhIL-6; SAA and CRP concentrations were elevated after stimulation with rhTNF-alpha.
  
  
  CONCLUSIONS
  We found that PCT and acute phase proteins such as CRP are induced by similar pathways. The liver appears to be a major source of PCT production. Thus, PCT may be considered an acute phase protein. The different kinetics of PCT, rather than a fundamentally different afferent pathway, may explain its putative diagnostic potential to discriminate bacterial infection from other causes of inflammation.
authors.affiliation: Department of Surgery, University Hospital Groningen, and the Groningen Institute for Drug Studies, The Netherlands. m.w.n.nijsten@chir.azg.nl
authors.forename: M W
authors.initials: MW
authors.lastname: Nijsten
authors.forename: P
authors.initials: P
authors.lastname: Olinga
authors.forename: T H
authors.initials: TH
authors.lastname: The
authors.forename: E G
authors.initials: EG
authors.lastname: de Vries
authors.forename: H S
authors.initials: HS
authors.lastname: Koops
authors.forename: G M
authors.initials: GM
authors.lastname: Groothuis
authors.forename: P C
authors.initials: PC
authors.lastname: Limburg
authors.forename: H J
authors.initials: HJ
authors.lastname: ten Duis
authors.forename: H
authors.initials: H
authors.lastname: Moshage
authors.forename: H J
authors.initials: HJ
authors.lastname: Hoekstra
authors.forename: J
authors.initials: J
authors.lastname: Bijzet
authors.forename: J H
authors.initials: JH
authors.lastname: Zwaveling
mesh_terms: D001424:Bacterial Infections / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000276:immunology* / Q000378:metabolism*; D002116:Calcitonin / Q000096:biosynthesis / Q000097:blood* / Q000737:chemistry / Q000276:immunology*; D015740:Calcitonin Gene-Related Peptide; D016002:Discriminant Analysis; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000150:complications* / Q000628:therapy*; D011446:Prospective Studies; D011498:Protein Precursors / Q000096:biosynthesis / Q000097:blood* / Q000737:chemistry / Q000276:immunology*; D015203:Reproducibility of Results; D000685:Serum Amyloid A Protein / Q000276:immunology* / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D015850:Interleukin-6; D011498:Protein Precursors; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide