Human and experimental septic shock are characterized by depletion of lipid droplets in the adrenals

Abstract

Cholesteryl ester deficiency which results in adrenal lipid store depletion has been proposed as a potential mechanism of sepsis associated adrenal insufficiency. We investigated histological abnormalities associated with sepsis in human and mice adrenals. From January 2006 to 2008, seven patients who died of septic shock and seven patients with rapidly fatal nonseptic illness were included. Adrenals were sampled within 12 h from death. Adrenals were also taken from 13 lipopolysaccharide (LPS)-challenged mice, 5 cecal ligation and puncture (CLP) mice and 5 controls. We semi-quantitatively analysed intensity of inflammation, necrosis, haemorrhage and lipid depletion. In patients, lipid depletion scores were significantly higher in septic shock than in controls (p = 0.011). In animals, lipid depletion was higher following LPS or CLP than in controls (p = 0.003). In adrenal cortex, in patients and not in animals, global scores for inflammation (p = 0.002), necrosis (p = 0.009) and haemorrhage (p = 0.009) were significantly higher in septic shock than in controls. Similarly, in zona fasciculata, in patients and not in animals, scores for inflammation (p = 0.007), necrosis (p = 0.023) and haemorrhage (p = 0.023) were significantly higher in septic shock than in controls. This study shows that diffuse lipid depletion in zona fasciculata is a hallmark of human septic shock, experimental endotoxaemia and sepsis. In patients, sepsis was associated with inflammation, necrosis and haemorrhage predominantly in zona fasciculata.