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Effects of gold on cytokine production in vitro; increase of monocyte dependent interleukin 10 production and
Jon Lampa1, Lars Klareskog, Johan Rönnelid
1Department of Rheumatology, Karolinska Institute, Stockholm, Sweden. jonlam@divmed.ks.se
Objective:
To investigate the effects of gold salt on the differential production of proinflammatory and antiinflammatory cytokines in vitro.
Methods:
Heparinized blood from 10 blood donors and 10 patients with polyarthritis was density separated and incubated with various concentrations of gold salt [Myocrisin gold sodium thiomalate (GSTM) plus phenyl mercury nitrate]. Cytokine production was measured after incubation for 16-20 h using an Elispot method detecting interleukin 10 (IL-10), IL-6, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) producing cells. In addition, parallel cell culture supernatants were collected and analyzed by ELISA for IL-10, IL-6, TNF-alpha, IFN-gamma, and IL-2. In some cultures phytohemagglutinin A (PHA) was added in predefined concentrations.
Results:
GSTM increased the number of cells producing IL-6 and IL-10 in a dose dependent manner, both with and without simultaneous addition of PHA. These effects were seen in samples from both healthy blood donors and patients with polyarthritis. The increase in IL-10 production was inhibited when monocytes were depleted. No effects of GSTM were seen on IFN-gamma or TNF-alpha producing cells. Parallel supernatant cultures displayed a GSTM dose dependent decrease in IFN-gamma levels after mitogen stimulation, whereas no changes were seen in IL-6 or TNF-alpha levels.
Conclusion:
The differential effects of gold salt on cytokine production, with a marked stimulatory effect on IL- 10 and IL-6, indicate that gold salt may act as a relatively selective immunostimulator rather than as a general immunosuppressant.