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AIM: The study aims to show that sodium selenite (SS) would have an immunomodulatory effect on the functional activity of proinflammatory macrophages (Mφs) during their extended extracellular activation at the onset of human type 1 diabetes (T1D). background: Exacerbated activation of proinflammatory “M1” macrophages (Mϕs) can promote chronic local pancreatic islet inflammation and T1D development. Background: Exacerbated activation of proinflammatory “M1” macrophages (Mϕs) can promote chronic local pancreatic islet inflammation and T1D development. Objective: We investigated the ex vivo effects of Ss on the immune modulation of global/extended activation of human proinflammatory M1-like Mϕs. Results: The levels of IL-1β, TNF-α, H2O2 and intracellular free calcium ions (ifCa2+), and the ratios of IL-1β-to-IL-10 and TNF-α-to-IL-10 were markedly increased in T1D Mϕs than in healthy control Mϕs. Conversely, both IL-10 production and arginase 1 (ARG1) activity were downregulated in T1D Mϕs. Additionally, Ss treatment induced a marked downregulation of respiratory burst, ifCa2+ levels, M1-like Mϕ-associated inducible nitric oxide (NO) synthase (iNOS) activity, cell necrosis and related necroinflammation biomarkers, including IL-1β and TNF-α, CD14 expression, and the ratios of iNOS-to-ARG1, IL-1β-to-IL-10, and TNF-α-to-IL-10. Moreover, Ss upregulated anti-inflammatory “M2-like” Mϕ activity as demonstrated by ARG1 activity and IL-10 production, as well as phagocytosis capacity. Conclusions: Ss exerts a potent immunomodulatory role on functional activities of human proinflammatory T1D M1-like Mϕs subjected to extended activation, as well as on the M1-like/M2-like dichotomy. Additionally, the current study provides a novel therapeutic approach using Ss to promote the anti-inflammatory function of Mϕs at the onset of T1D.

Objectives: We examined the influence of the ex vivo combination therapy of metformin (Met, 1,1-dimethylbiguanide hydrochloride) with sodium selenite (Ss, Na2SeO3) on the changes in the production of nitric oxide (NO) and selected cytokines by circulating monocytes (MOs) during T-cell acute lymphoblastic leukemia (T-ALL). Methods: Assays were performed on MO cell samples isolated from children with T-ALL. Results: Met+Ss combination therapy reversed the Ss effect on the upregulation of NO production. Both Met+Ss and Ss treatment alone induced a significant downregulation of extracellular calcium ions consumption (ecCa2+) levels. Additionally, Met treatment induced a significant upregulation of IL-1β and TNF-α production; such effects were significantly reversed after combination with Ss treatment. Moreover, Met+Ss induced no significant effect on the production of IL-10, IL-6 and TNF-α, but a slight increase in IFN-γ levels. Furthermore, treatment with Ss alone induced a slight increase of IFN-γ. Finally, Met+Ss induced a marked upregulation of relative Bcl-2 expression in MOs. Conclusions: Met+Ss combination therapy results in downregulation of NO production, IL-1β and TNF-α release as well as in upregulation of the relative expression levels of Bcl-2-associated survival of primary MOs in human T-ALL.