Corticosteroid-binding globulin: acute and chronic inflammation

ABSTRACT

Introduction: Corticosteroid-binding globulin (CBG) is the principal transport protein for cortisol binding 80% in a 1:1 ratio. Since its discovery in 1958, CBG’s primary function has been considered to be cortisol transport within the circulation. More recent data indicate a cortisol tissue delivery function, particularly at inflammatory sites. CBG’s structure as a non-inhibitory serine protease inhibitor allows allosteric structural change after reactive central loop (RCL) cleavage by neutrophil elastase (NE) and RCL insertion into CBG’s protein core. Transition from the high to low affinity CBG form reduces cortisol-binding.

Areas covered: In acute systemic inflammation, high affinity CBG (haCBG) is depleted proportionate to sepsis severity, with lowest levels seen in non-survivors. Conversely, in chronic inflammation, CBG cleavage is paradoxically reduced in proportion to disease severity, implying impaired targeted delivery of cortisol. CBG’s structure allows thermosensitive release of bound cortisol, by reversible partial insertion of the RCL and loosening of CBG:cortisol binding. Recent studies indicate a significant frequency of function-altering single nucleotide polymorphisms of the SERPINA6 gene which may be important in population risk of inflammatory disease.

Expert commentary: Further exploration of CBG in inflammatory disease may offer new avenues for treatment based on the model of optimal cortisol tissue delivery.

KEYWORDS:

• Cortisol
• high-affinity CBG
• low-affinity CBG
• inflammation
• corticosteroid-binding globulin

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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Funding

This article was not funded.