The Effect of Short-Term Hyperglycemia on the Innate Immune System

Background: Diabetes mellitus increases the susceptibility to infection by altering both the innate and the adaptive immune systems. Hyperglycemia has been associated with adverse outcomes in hospitalized patients, especially critically ill patients; these poor outcomes are explained in part by hospital-associated infections.

Materials and methods: PubMed, EMBASE and Google Scholar were searched to identify studies published between 1970 and 2014 reporting short-term effects of hyperglycemia on the innate immune system. MeSH database search terms included hyperglycemia, immune system, inflammation, inflammation mediators, neutrophils, endothelial dysfunction, complement system proteins and diabetes. Pertinent articles reported studies in healthy volunteers and diabetic patients, using in vitro laboratory experiments, and with animal models.

Results: Hyperglycemia activates protein kinase C, and this inhibits neutrophil migration, phagocytosis, superoxide production and microbial killing. High glucose concentrations decrease the formation of neutrophil extracellular traps. Hyperglycemia can also induce Toll-like receptor expression and inhibit neutrophil function and apoptosis. High glucose concentrations decrease vascular dilation and increase permeability during the initial inflammatory responses, possibly through protein kinase C activation. Hyperglycemia can cause direct glycosylation of proteins and alter the tertiary structure of complement; these changes inhibit immunoglobulin-mediated opsonization of bacteria and complement fixation to bacteria and decreases phagocytosis. Hyperglycemia also stimulates the production and release of cytokines. Several trials have demonstrated that better glycemic control reduces nosocomial infections in critically ill patients and surgical site infections.

Conclusions: In summary, acute hyperglycemia can significantly alter innate immune responses to infection, and this potentially explains some of the poor outcomes in hospitalized patients who develop hyperglycemia.