Elevated blood levels of the proinflammatory
cytokines interleukin-6 (IL-6),
interleukin-8 (IL-8), and MCP-1 (
monocyte chemoattractant protein-1) increase
insulin resistance and the risk of
cardiovascular disease (CVD). There is no previous study that has examined the effect of
ketosis and trivalent
chromium on
IL-6,
IL-8, or MCP-1 secretion in any cell type or in human or animal model. The authors examined the hypothesis that
ketosis increases and trivalent
chromium decreases the levels of
cytokines and oxidative stress in diabetes using a U937 monocyte cell culture model. Cells were cultured with control, high
glucose (HG), and
acetoacetate (AA) in the absence or presence (0.5-10 microM) of CrCl(3),
chromium picolinate (Cr-P), or
chromium niacinate (Cr-N) at 37 degrees C for 24 h. The data show a significant stimulation of
IL-6,
IL-8, and MCP-1 secretion and an increase in oxidative stress in cells treated with HG or AA. The effect of HG on
cytokine secretion was reduced by Cr-N, and to a lesser extent by CrCl(3) and Cr-P. The effect of HG on oxidative stress was reduced by Cr-N and CrCl 3, but not by Cr-P. Similarly, Cr-N decreased the
cytokine secretion in HG + AA-treated cells. Cr-N significantly decreased standard
oxidant (H(2)O(2)) induced
cytokine secretion, which suggests that reduction of
cytokine secretion by Cr-N is in part mediated by its antioxidative effect. In a cell culture model, Cr-N appears to be the most effective form of
chromium in inhibiting oxidative stress and proinflammatory
cytokine secretion by monocytes. This study suggests that
chromium niacinate supplementation may be useful in reducing vascular
inflammation and the risk of CVD in diabetes.