Lucigenin-enhanced chemiluminescence was examined as an index of neutrophil
superoxide production in four groups of 20 subjects: controls with/without
infection and type 1 diabetics with/without
infection. At 5 mM
glucose there was no significant difference in chemiluminescence output between neutrophils from the four groups (P greater than 0.01). Increasing the in vitro
glucose concentration from 5 to 20 mM produced an 8.75% reduction in
superoxide in the combined control groups, compared with a 21.45% reduction in the diabetic subjects (P less than 0.01). With the addition of an
aldose reductase inhibitor (
Statil, ICI) to neutrophils from diabetic subjects, the suppression caused by an increase in
glucose concentration to 20 mM was reduced to 4.5%. This value was similar to the controls (P greater than 0.01). Neutrophil
aldose reductase activity, measured in 28 diabetic subjects was 0.024 +/- 0.003 U/10(8) cells (mean +/- SE). There was a significant correlation between
aldose reductase activity and
superoxide suppression (P less than 0.01, r = 0.64). These results suggest that
aldose reductase is responsible for reduced
superoxide production in diabetic patients and the addition of an
aldose reductase inhibitor to the diabetic neutrophil restores
superoxide output to control values.