Cortisol-binding globulin cleavage at sites of inflammation in critically ill patients
© Williams et al; licensee BioMed Central Ltd. 2009
Published: 13 March 2009
In vitro studies have shown that cortisol-binding globulin (CBG) can be cleaved by neutrophil elastase with a resulting reduction in affinity for cortisol . Local elastase production by activated neutrophils may trigger cortisol release by CBG cleavage, providing a potential mechanism for targeted delivery of corticosteroids to inflamed tissues. We looked for evidence of this process at sites of inflammation in critically ill patients.
Sera and bronchoalveolar lavage (BAL) fluid were collected from six mechanically ventilated patients with a clinical diagnosis of ventilator-associated pneumonia or acute respiratory distress syndrome (ARDS). These samples, along with sera from six healthy controls, were subjected to gel electrophoresis (SDS-PAGE) and immunoblotting for CBG. Densitometry was used to quantify the proportion of cleaved CBG.
This study provides the first in vivo support for a mechanism of enhanced cortisol delivery to sites of inflammation that involves local CBG cleavage.
Study supported by the Intensive Care Society (UK).