Anti-rheumatic gold compounds as sublethal modulators of monocytic LPS-induced cytokine secretion
Journal
Toxicology in Vitro
Journal Volume
19
Journal Issue
3
Pages
365-371
Date Issued
2005
Author(s)
Abstract
The objective of this study was to quantify the ability of sublethal concentrations of several gold compounds to differentially modulate the monocytic secretion of key cytokines that are important in the etiology of rheumatic diseases. Human THP1 monocytic cells were exposed to the anti-rheumatic drugs auranofin (AF), gold sodium thiomalate (GSTM) or HAuCl 4 (Au(III)) for 24-72 h. Succinate dehydrogenase (SDH) activity of the monocytes was used to determine sublethal concentrations. Monocytes were then exposed to sublethal concentrations of gold compounds for 72 h, and the activator lipopolysaccharide (LPS) was added (or not) to cultures for the last 6 h. The secretion of IL6, IL8, IL10, and TNFα were measured in cell supernatants using ELISA. Cytokine secretion was compared among concentrations and gold compounds. SDH experiments established a sublethal concentration range of 0-75 μM for GSTM and Au(III) and 0-0.5 μM for AF. In cytokine experiments, none of the compounds alone activated secretion of any of the cytokines, but all differentially (50-440%, p < 0.05) increased LPS-induced secretion of IL6 and IL8 over TNFα and IL10. In conclusion, sublethal concentrations of AF, GSTM, and Au(III) all may differentially modulate activation of monocytic cells, and this differential modulation may be important in the mechanisms of action of these compounds. ? 2004 Elsevier Ltd. All rights reserved.
Subjects
Arthritis; Cytokines; Metal compounds; Toxicity
SDGs
Other Subjects
antirheumatic agent; auranofin; aurothiomalate; cytokine; gold chloride; gold derivative; interleukin 10; interleukin 6; interleukin 8; lipopolysaccharide; succinate dehydrogenase; tumor necrosis factor alpha; article; concentration response; controlled study; cytokine release; cytotoxicity; enzyme activity; enzyme linked immunosorbent assay; human; human cell; human cell culture; monocyte; rheumatic disease; supernatant
Publisher
Elsevier Ltd
Type
journal article