The Effects of Diabetes Mellitus and in Vitro Hyperglycemia On Cytokine Secretion From Peripheral Blood Leucocytes

We wanted to study the separate effects of in vitro hyperglycemia and uncontrolled diabetes mellitus on the capability of stimulated peripheral blood mononuclear cells to produce cytokines. PMNCs of 20 uncontrolled diabetic patients (8 type I and 12 type II) and 12 healthy subjects were cultured in vitro in four different glucose concentrations (0, 100, 300, and 600 mg/dl) and stimulated with lipopolysaccharides (LPS). Then the levels of the following cytokines: tumor necrosis factor α (TNFα), interleukin6 (IL6), interleukin10 (IL10), and interleukin12 (IL12) were measured by enzyme linked immunosorbent assay (ELISA) in the cell culture supernatants. We found that the LPS stimulated synthesis of TNFα, IL6, IL10, and IL12 by human PMNCs was increased by high and absence of glucose. Diabetes mellitus failed to cause significant increase in the LPS stimulated production of TNFα, IL6, and IL10, but enhanced significantly the production of IL12 compared to controls. Type I diabetic cells produced higher amount of IL12 than controls. There was no significant difference between type I, type II, and control PMNCs capability production of TNF, IL6, and IL10. We suggest that acute hyperglycemia is a major cause of excessive cytokine production rather than diabetes mellitus itself, so glycaemic control may modify cytokine production and inflammatory process in diabetic patients. Also, IL-12 is more susceptible for increased production by hyperglycemia than the other cytokines of TNFα, IL-6 and IL-10.