title: Corticosteroid-binding globulin cleavage may be pathogen-dependent in bloodstream infection.
abstract: OBJECTIVE
  The process of enzymatic cleavage of high- to low-affinity corticosteroid-binding globulin (haCBG to laCBG) by neutrophil elastase leads to local tissue release of cortisol. Recently Pseudomonas aeruginosa was shown to instigate CBG cleavage with release of free cortisol in vitro. Hence, CBG cleavage with release of anti-inflammatory cortisol in infection may be pathogen-dependent. Our objective was to determine whether haCBG and laCBG levels are altered in infected patients compared with controls, and whether these alterations were particular to causative bacteria.
  
  
  METHODS
  An observational, cross-sectional study at a public pathology institution and tertiary hospital in Adelaide, South Australia.
  
  
  METHODS
  100 positive blood culture samples and 100 healthy control samples were analysed for serum total CBG, haCBG, laCBG, total and free cortisol, leukocyte and neutrophil count, C-reactive protein and Pitt severity score.
  
  
  RESULTS
  Patients with infection had lower serum total CBG, haCBG and laCBG, all P<0.0001, than healthy controls. This was true in patients with and without a systemic inflammatory response and in those with culture-positive and culture-negative infections. Pseudomonas aeruginosa infection was associated with the lowest total and laCBG levels of the pathogen groups despite having the lowest inflammatory markers.
  
  
  CONCLUSIONS
  There was evidence of CBG cleavage in early infection both in patients with and without systemic inflammation and regardless of culture status. Pseudomonas infection appeared to enhance cleavage. This observation, along with cleavage in severe neutropenia suggests mechanisms other than neutrophil elastase may be involved in CBG cleavage and local tissue cortisol release in infection.
authors.affiliation: Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia; Discipline of Medicine, University of Adelaide, Adelaide, SA 5000, Australia. Electronic address: Marni.Nenke@health.sa.gov.au.
authors.forename: Marni A
authors.initials: MA
authors.lastname: Nenke
authors.affiliation: Steroid & Immunobiochemistry Laboratory, Canterbury Health Laboratories, Christchurch, New Zealand.
authors.forename: John G
authors.initials: JG
authors.lastname: Lewis
authors.affiliation: Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia; Discipline of Medicine, University of Adelaide, Adelaide, SA 5000, Australia; Chemical Pathology Directorate, SA Pathology, Adelaide, SA 5000, Australia.
authors.forename: Wayne
authors.initials: W
authors.lastname: Rankin
authors.affiliation: Infectious Diseases Clinical Service, Royal Adelaide Hospital, Adelaide, SA 5000, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Shaw
authors.affiliation: Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia; Discipline of Medicine, University of Adelaide, Adelaide, SA 5000, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Torpy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000097:blood / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology; D059748:Proteolysis; D011552:Pseudomonas Infections / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D014156:Transcortin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D002097:C-Reactive Protein; D014156:Transcortin; D006854:Hydrocortisone
keywords: Corticoseroid-binding globulin; Cortisol; High-affinity CBG; Infection; Inflammation; Pseudomonas