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DOI: 10.1016/j.homp.2015.12.058
Differential dose-dependent effects of arsenic in pro- and anti-inflammatory cytokines
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Publication History
Publication Date:
27 January 2018 (online)
Introduction : Arsenic is known to exert detrimental effects at high doses, due to its action on multiple cellular pathways and epigenetics. Conversely, arsenic-containing agents have been in medicinal use and Arsenicum album is widely used homeopathic drug. Lymphocytes, monocytes/macrophages are major targets of Arsenicum album and homeopathic Materia Medica associates it also to inflammation and blood alterations. Inorganic arsenic (NaAsO2, iAs) has reported multifaceted actions at cell level, that depend on the doses, the time and the type of cells.
Methods : In this study the effect of iAs on human monocytic leukemia cell line THP-1 was analyzed. Dose response experiments have been conducted using iAs concentrations from 10−10 Mol/L to 5 × 10−3 Mol/L for 24 h with THP-1, cells differentiated into activated macrophages by phorbol (PMA) exposure and primed with the endotoxin LPS (10 ng/ml). Proinflammatory (TNF-a and IL-1β) and anti-inflammatory (IL-10) cytokines expression was monitored, while variation of viability and cell density were examined by WST assay.
Results : THP-1 cell metabolic activity dropped to 20% of the control after 24 h exposure to 10−4 Mol/L iAs, while lower concentrations did not affect the viability. Cell survival was not improved after pre-sensitization of the cells for short times (2–3 h) with sub lethal doses of iAs. Pro-inflammatory cytokines Il-1b and TNF-a showed hormetic-like dose-response with peaks around 10−6 to 10−5 Mol/L iAs, while the anti-inflammatory cytokine IL-10 was downregulated by iAs in dose-dependent fashion. These results suggest different signal pathways engaged by arsenic in macrophage cells. Little effects of Arsenicum album high dilutions were found in the THP-1 cellular model explored so far. Further results will come from the analysis of other biomarkers involved in inflammation and stress response signaling under Arsenicum album conditioning in THP-1 and other primary immune cells.