Neutrophil sorbitol production impairs oxidative killing in diabetes

The mechanism whereby hyperglycaemia inhibits neutrophil function is unclear. We have examined neutrophil killing of Candida albicans in the presence of increased concentrations of glucose and galactose. Killing was abolished in 50 mmol/l glucose and 10 and 50 mmol/l galactose. The oxidative phase of killing was examined using lucigenin-enhanced chemiluminescence. An increase in glucose concentration from 5 to 50 mmol/l produced a fall in chemiluminescence output from 128.5 +/- 16.8 (mean +/- SE) to 82.2 +/- 9.8 mV min (a reduction of 36%). These data suggest the existence of aldose reductase activity in neutrophils and using gas chromatography we have demonstrated the presence of sorbitol in extracts of diabetic neutrophils. As oxidative killing and sorbitol production are both NADPH-dependent the inhibition of killing is likely to be due to competition for this electron donor. This abnormality of neutrophil function may aggravate various infections in the patient with diabetes.