Acute hyperglycemia and the innate immune system: Clinical, cellular, and molecular aspects

Objective: To extract from the biomedical literature the reported effects of acute hyperglycemia on the major components of the innate immune system and to describe the clinical benefits of strict blood glucose control in certain patients. Data Source and Selection: A Medline/PubMed search (1966 to July 2004) with manual cross-referencing was conducted, including all relevant articles investigating the effects of acutely elevated glucose levels on innate immunity. All publication types, languages, or subsets were searched. \Data Extraction and Synthesis: Original and selected review articles, short communications, letters to the editor, and chapters of selected textbooks were extracted. Most recent and relevant clinical trials were reviewed for the introductory section to provide the clinical background to this topic. The selected bench laboratory articles were then divided into three main categories based on the timing of events: a) the early phase of the innate immune reaction; b) the cytokine network; and c) the phagocytic phase. The most obvious findings related to hyperglycemia included reduced neutrophil activity (e.g., chemotaxis, formation of reactive oxygen species, phagocytosis of bacteria), despite accelerated diapedesis of leukocytes into peripheral tissue, as well as specific alterations of cytokine patterns with increased concentrations of the early proinflammatory cytokines tumor necrosis factor-alpha and interieukin-6. Furthermore, a reduction of endothelial nitric oxide formation takes place, thus decreasing microvascular reactivity to dilating agents such as bradykinin, and complement function (e.g., opsonization, chemotaxis) is impaired, despite elevations of certain complement factors. Conclusions: Acute, short-term hyperglycemia affects all major components of innate immunity and impairs the ability of the host to combat infection, even though certain distinctive proinflammatory alterations of the immune response can be observed under these conditions.