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

Area of Science:

• Endocrinology
• Infectious Diseases
• Immunology

Background:

• Enzymatic cleavage of high-affinity corticosteroid-binding globulin (haCBG) to low-affinity (laCBG) by neutrophil elastase releases cortisol.
• Pseudomonas aeruginosa can induce CBG cleavage, releasing free cortisol in vitro, suggesting pathogen-dependent effects.

Purpose of the Study:

• To investigate alterations in haCBG and laCBG levels in infected patients compared to controls.
• To determine if these alterations are specific to the causative bacteria.

Main Methods:

• Observational, cross-sectional study involving 100 infected patients and 100 healthy controls.
• Analysis of serum total CBG, haCBG, laCBG, total and free cortisol, leukocyte and neutrophil counts, C-reactive protein, and Pitt severity score.

Main Results:

• Infected patients exhibited significantly lower serum total CBG, haCBG, and laCBG compared to controls (P<0.0001).
• These reductions were observed regardless of systemic inflammatory response or infection culture status.
• Pseudomonas aeruginosa infection was associated with the lowest total and laCBG levels, despite lower inflammatory markers.

Conclusions:

• Evidence of CBG cleavage and cortisol release occurs in early infection, irrespective of systemic inflammation or culture status.
• Pseudomonas infection appears to enhance CBG cleavage.
• Cleavage in severe neutropenia suggests non-neutrophil elastase mechanisms may contribute to cortisol release in infection.