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Hyperglycemia and changes in osmolarity lead to an increase in IL-6 and IL-1β cytokine production of human peripheral blood mononuclear cells in vitro

Introduction

Acute hyperglycemia and insulin resistance are characteristics of metabolic and endocrine imbalances of critically ill patients and are subject to a substantial inflammatory response that is partly mediated by cytokines produced by peripheral blood mononuclear cells (PBMC). Treatment with intensive insulin therapy to keep patients normoglycemic has been shown to reduce inflammatory responses. It is unclear whether hyper-glycemia, insulin or osmolarity changes exert direct effects on proinflammatory cytokines. We investigated the direct effects of these substances on cytokine production of PBMC in vitro.

Methods

PBMC were isolated from peripheral blood of 10 healthy volunteers via Ficoll gradient. Cells were incubated for 3 hours at 37°C with/without low/high concentrations of glucose, mannitol, urea, insulin and stimulated with 0.5 ng/ml LPS. After 24 hours, concentrations of IL-6 and IL-1β were measured with an ELISA method.

Results

Increasing concentrations of glucose, mannitol and urea resulted in a significant increase of IL-6 and IL-1β cytokine production. Insulin had no effect (Table 1).

Table 1 Table 1

Conclusion

High concentrations of glucose, mannitol and urea lead to a significant increase in IL-6 and IL-1β cytokine production by PBMC in vitro. The most profound effect was seen with hyperglycemia. Besides hyperglycemia, also uremia and high osmolarity seem to augment inflammation. Insulin could not reverse the increase in inflammation. These findings may be relevant in explaining the beneficial effects of normoglycemia on the inflammatory response in critically ill patients.

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Otto, N., Schindler, R., Frei, U. et al. Hyperglycemia and changes in osmolarity lead to an increase in IL-6 and IL-1β cytokine production of human peripheral blood mononuclear cells in vitro. Crit Care 11, P122 (2007). https://0-doi-org.brum.beds.ac.uk/10.1186/cc5282

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Keywords

  • Urea
  • Insulin Resistance
  • Inflammatory Response
  • Mannitol
  • Peripheral Blood Mononuclear Cell