Stress hyperglycemia, insulin treatment, and innate immune cells

Abstract

Hyperglycemia (HG) and insulin resistance are the hallmarks of a profoundly altered metabolism in critical illness resulting from the release of cortisol, catecholamines, and cytokines, as well as glucagon and growth hormone. Recent studies have proposed a fundamental role of the immune system towards the development of insulin resistance in traumatic patients. A comprehensive review of published literatures on the effects of hyperglycemia and insulin on innate immunity in critical illness was conducted. This review explored the interaction between the innate immune system and trauma-induced hypermetabolism, while providing greater insight into unraveling the relationship between innate immune cells and hyperglycemia. Critical illness substantially disturbs glucose metabolism resulting in a state of hyperglycemia. Alterations in glucose and insulin regulation affect the immune function of cellular components comprising the innate immunity system. Innate immune system dysfunction via hyperglycemia is associated with a higher morbidity and mortality in critical illness. Along with others, we hypothesize that reduction in morbidity and mortality observed in patients receiving insulin treatment is partially due to its effect on the attenuation of the immune response. However, there still remains substantial controversy regarding moderate versus intensive insulin treatment. Future studies need to determine the integrated effects of HG and insulin on the regulation of innate immunity in order to provide more effective insulin treatment regimen for these patients.

Figure 1

Schematic summary of hyperglycemia and insulin treatment regulation of innate immune cells. Overwhelming stress resulted from critical illness, such as severe burn, major surgery, or sepsis stimulates the release of cortisol, catecholamines, glucagon, and growth hormone, which increase hepatic glucose production and impair glucose consumption by peripheral tissues. Long-term stress-induced hyperglycemia induces hyperproinflammatory responses and depressed cell functions, which is linked to increased risk of mortality and morbidity. Insulin plays a different role in regulating innate immune cells including monocytes, macrophages, and neutrophils. It generally improves their cellular activities and attenuates their inflammatory responses.