Corticosteroid-binding globulin cleavage may be pathogen-dependent in bloodstream infection

Abstract

ObjectiveThe 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. DesignAn observational, cross-sectional study at a public pathology institution and tertiary hospital in Adelaide, South Australia. Methods100 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. ResultsPatients 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. ConclusionsThere 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.