High glucose concentrations increase the tumor necrosis factor-alpha production capacity by human peripheral blood mononuclear cells.

ABSTRACT

The proinflammatory cytokines tumor necrosis factor-a (TNF) and interleukin-1b (IL-1) play an important role in the pathogenesis of insulin-dependent diabetes mellitus, while TNF is also involved in promoting insulin resistance. It has been recently shown that glucose can induce the synthesis of TNF and IL-6 in human monocytes. The aim of the present study was to investigate the effect of glucose on unstimulated and lipopolysaccharide (LPS)-induced TNF and IL-1 production by human peripheral blood mononuclear cells (PBMC). No effect of glucose on spontaneous release of TNF or IL-I could be observed. The LPS-stimulated production of TNF was enhanced when cells were preincubated with increasing glucose concentrations. In contrast, no effect of glucose preincubation on LPS-induced IL-I synthesis was found. In conclusion, high glucose concentrations can increase the stimulated TNF production capacity, with possible important consequences for patients with diabetes mellitus.