Inflammatory Status of Monocytes in Type 2 Diabetes Mellitus

Сhronic inflammation is considered as a key factor in the development of type 2 diabetes mellitus. Impaired tolerance of the inflammatory response of monocytes is regarded as an important mechanism in the pathogenesis of chronic inflammation. In this work, we study the inflammatory activation and tolerance  of the immune response of monocytes in diabetes. In total, 40 patients with newly diagnosed diabetes   and 40 control group participants were included in the study. The level of basal, LPS-stimulated and re-stimulated secretion of the TNF-α, IL-1β, and MCP-1 cytokines was assessed in a monocyte culture isolated from the blood by immunomagnetic separation of CD14+ cells. The level of basal, LPS-stimulated and re-stimulated TNF-α secretion was significantly higher in patients with diabetes; the level of IL-1β secretion did not differ significantly between the groups; basal and re-stimulated MCP-1 secretion was also significantly higher in the diabetes group. Re-stimulated secretion of TNF-α and IL-1β was reduced compared to primary-stimulated secretion in both groups, demonstrating the tolerance of the macrophage immune response to these cytokines. Re-stimulated secretion of MCP-1 in 42% of diabetes patients was higher than primary stimulated secretion, thus revealing an impaired tolerance of the immune response of macrophages. A correlation was found between TNF-α secretion and body mass index, r=0.631, p<0.001, and with glycemic level, r=0.427, p=0.037. The results obtained demonstrate inflammatory activation     of monocytes with hypersecretion of TNF-α and MCP-1, impaired tolerance of the immune response of monocytes in diabetes regarding the secretion of MCP-1, as well as a correlation of TNF-α secretion   with body mass index and glycemic level. This indicates an important role of TNF-α and MCP-1 in the pathogenesis of chronic inflammation in type 2 diabetes, thus allowing these cytokines to be considered as potential therapeutic targets for pathogenetic therapy of type 2 diabetes.