Effects of gold on cytokine production in vitro; increase of monocyte dependent interleukin 10 production and decrease of interferon-gamma levels.
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.


CONCLUSIONS
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.
Lampa
Jon
J
Department of Rheumatology, Karolinska Institute, Stockholm, Sweden. jonlam@divmed.ks.se
Klareskog
Lars
L
Rönnelid
Johan
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000276:immunology; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050607:Organogold Compounds; D015854:Up-Regulation / Q000187:drug effects* / Q000276:immunology
D000954:Antigens, Surface; D018501:Antirheumatic Agents; D007376:Interleukin-2; D015850:Interleukin-6; D050607:Organogold Compounds; D016753:Interleukin-10; D007371:Interferon-gamma