title: Mortality is increased by procalcitonin and decreased by an antiserum reactive to procalcitonin in experimental sepsis.
abstract: OBJECTIVE
  Procalcitonin (ProCT), the precursor to the calcitonin hormone, is abnormally increased in experimental and clinical systemic inflammation, including sepsis. Initially, we investigated the effects of supraphysiologic amounts of ProCT administered to animals with septic peritonitis. Subsequently, we evaluated the efficacy of prophylactic and therapeutic immune blockade of ProCT in this lethal model of sepsis.
  
  
  METHODS
  Prospective, experimental, controlled study.
  
  
  METHODS
  Animal research laboratory approved by the American Association for the Accreditation of Laboratory Animal Care at a Veterans Affairs Medical Center.
  
  
  METHODS
  Young male Golden Syrian hamsters, weighing 90 to 120 g.
  
  
  METHODS
  In the first study, serum ProCT concentrations were measured in animals at 0, 3, 6, 12, and 24 hrs after induction of sepsis by intraperitoneal implantation of pellets containing Escherichia coli (5 x 10(8) colony-forming units/pellet). In the second study, with mortality as the end point, 30 microg/kg of isolated, purified human ProCT in 10% hamster serum (experimental) or an equal volume of 10% hamster serum (control) were administered intravenously at the time of the E. coli peritoneal implantation. In the third study, experimental animals received intraperitoneal injections of a multiregion-specific goat antiserum reactive to hamster ProCT 1 hr before and 24 hrs after E. coli implantation, while control animals received nonimmune goat serum at the same time points. In the final study, the same antiserum was administered in five divided doses during the 24 hrs after the insertion of E. coli.
  
  
  RESULTS
  In the initial study, ProCT concentrations were increased shortly after induction of sepsis and peaked at 12 hrs. Administration of exogenous ProCT to septic animals significantly increased mortality compared with control animals (93% vs. 43%, p=.02). Prophylactic blockade of ProCT almost completely protected the animals from the lethal effects of sepsis: the 102-hr mortality rate in the experimental group was 6% compared with 62% in the control group (p < .003). In the therapeutic trial, the 102-hr mortality rate was 54% in experimental animals compared with 82% in control animals (p < .045).
  
  
  CONCLUSIONS
  These results demonstrate that increased ProCT exacerbates mortality in experimental sepsis, whereas neutralization of ProCT increases survival. Thus, ProCT, in addition to being an important marker of severity of systemic inflammation and mortality, is an integral part of the inflammatory process and directly affects the outcome.
authors.affiliation: Department of Medicine, VA Medical Center, Washington, DC 20422, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Nylen
authors.forename: K T
authors.initials: KT
authors.lastname: Whang
authors.forename: R H
authors.initials: RH
authors.lastname: Snider
authors.forename: P M
authors.initials: PM
authors.lastname: Steinwald
authors.forename: J C
authors.initials: JC
authors.lastname: White
authors.forename: K L
authors.initials: KL
authors.lastname: Becker
mesh_terms: D000818:Animals; D002116:Calcitonin / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology / Q000633:toxicity*; D015740:Calcitonin Gene-Related Peptide; D006224:Cricetinae; D004927:Escherichia coli Infections / Q000628:therapy; D006801:Humans; D007106:Immune Sera / Q000008:administration & dosage*; D007116:Immunization, Passive; D007274:Injections, Intraperitoneal; D008297:Male; D008647:Mesocricetus; D011498:Protein Precursors / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology / Q000633:toxicity*; D018805:Sepsis / Q000097:blood / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*
chemical_list: C000606589:CALCA protein, human; D007106:Immune Sera; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide