Decreased production of inflammatory cytokines by circulating monocytes and dendritic cells in type 2 diabetic men with atherosclerotic complications

Antigen-presenting cells (APCs) are involved in the development of atherosclerosis, whose complications represent the main cause of death in diabetic patients. Nevertheless, their role in atherogenesis is poorly understood. We compared the number of circulating monocyte and dendritic cell (DC) subsets as well as their capacity to produce inflammatory cytokines IL-1 beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in type 2 diabetic men with (n = 11) and without (n = 44) chronic atherosclerotic complications. Identification and enumeration of peripheral blood (PB) lymphoid subsets, monocytes, myeloid (CD33(strong+)), CD16(+), and plasmacytoid (CD33(-/dim+)) DCs as well as of their spontaneous and stimulated production of IL-1 beta, IL-6, and TNF-alpha were performed at the single-cell level by flow cytometry. Our results show that type 2 diabetic men with atherosclerotic complications display a significantly reduced spontaneous secretion of IL-6 by monocytes and CD16(+) DCs and of TNF-alpha by CD16(+) DCs as compared to patients without atherosclerotic complications. Spontaneous secretion of IL-1 beta by monocytes and CD16(+) DCs and of IL-6 by CD33(+) and plasmacytoid DCs was detected in patients without atherosclerotic complications but not in the other patients with complications. Taken together, these results indicate that type 2 diabetic men with atherosclerotic complications display both quantitatively and functionally impaired immunological responses by circulating APCs. The decreased patterns of inflammatory cytokine production by these cells may influence the inflammatory response mediated by APCs as well as the antigen-specific responses mediated by other cells such as T cells. (c) 2007 Elsevier Inc. All rights reserved.