Inhibition of Human Natural Killer Cell Function in vitro by Glucose Concentrations Seen in Poorly Controlled Diabetes

Type 1 and type 2 diabetes mellitus are associated with an increased risk of viral infections and certain tumors. Natural killer (NK) cells appear to have a central role in the immune defense against viral infection as well as tumor cells, and impairment of NK function could result in an increased incidence of infection or tumors. We show that exposure of NK cells to elevated glucose concentrations (in the range seen in poorly controlled diabetes) results in a significant inhibition of their cytolytic function. When glucose is elevated to 44 mM (800 mg/dl), there is a 59% decrease in NK cytolytic function compared to that seen when glucose is in the normal range (4.4-5.5 mM). Specific lysis is inhibited by 42% by 33 mM glucose, and 22 mM glucose produce a 31 % inhibition of specific lysis. This inhibition is not due to a disruption of NK cell binding to target cells. The effect is reversible under the in vitro conditions used, indicating that it is not due to the glycation of proteins that can occur with elevated glucose levels. Exposure of NK cells to 44 mM glucose results in a significant elevation of cAMP, indicating that elevation of this potent inhibitor of NK cytolysis may be in part responsible for the glucose-induced inhibition of NK function.