Resistin and the proinflammatory cytokines, such as TNF-alpha, IL-6, and
IL-1 beta, produced by adipocytes, and macrophages, are considered to be
important modulators of chronic inflammation contributing to the
development of obesity and atherosclerosis. Human monocyte-enriched
mononuclear cells, from ten healthy individuals, were exposed to high
concentrations of insulin, leptin, and glucose (alone or in combination)
for 24 hours in vitro. Resistin, TNF-alpha, IL-6, and IL-1 beta
production was examined and compared to that in untreated cells. High
insulin and leptin concentrations significantly upregulated resistin and
the cytokines. The subseuent addition of high glucose significantly
upregulated resistin and TNF-alpha mRNA and protein secretion, while it
did not have any effect on IL-6 or IL-1 beta production. By comparison,
exposure to dexamethasone reduced TNF-alpha, IL-6, and IL-1 beta
production, while at this time point it increased resistin protein
secretion. These data suggest that the expression of resistin,
TNF-alpha, IL-6, and IL-1 beta from human mononuclear cells, might be
enhanced by the hyperinsulinemia and hyperleptinemia and possibly by the
hyperglycemia in metabolic diseases as obesity, type 2 diabetes, and
atherosclerosis. Therefore, the above increased production may
contribute to detrimental effects of their increased adipocyte-derived
circulating levels on systemic inflammation, insulin sensitivity, and
endothelial function of these patients
