Hig� Insulin and �eptin Increase Resistin and In�ammatory Cytokine Production fromHumanMononuclear Cells

Resistin and the proin�ammatory cytokines, such as TNF-αα, IL-6, and IL-1ββ, produced by adipocytes, and macrophages, are considered to be important modulators of chronic in�ammation contributing to the development of obesity and atherosclerosis. Humanmonocyte-enrichedmononuclear 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-αα, IL-6, and IL-1ββ production was examined and compared to that in untreated cells. High insulin and leptin concentrations signi�cantly upregulated resistin and the cytokines. e subse�uent addition of high glucose signi�cantly upregulated resistin and TNF-αα mRNA and protein secretion, while it did not have any effect on IL-6 or IL-1ββ production. By comparison, exposure to dexamethasone reduced TNF-αα, IL-6, and IL-1ββ production, while at this time point it increased resistin protein secretion.ese data suggest that the expression of resistin, TNF-αα, IL-6, and IL-1ββ 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. erefore, the above increased production may contribute to detrimental effects of their increased adipocyte-derived circulating levels on systemic in�ammation, insulin sensitivity, and endothelial function of these patients.