Abstract
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.
Key Indexing Terms
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Article info
Publication history
Accepted:
September 8,
2015
Received:
July 15,
2015
Footnotes
The authors have no financial or other conflicts of interest to disclose.
Identification
Copyright
© 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
