Evidence for immunostimulatory effects of intramuscular gold in patients with rheumatoid arthritis: correlation with skin reactions
Ernestam, S.; Lampa, J.; Rogberg, S.; Rönnelid, J.; Klareskog, L.; Hafström, Iäld.
Journal of Rheumatology 30(8): 1748-1755
2003
ISSN/ISBN: 0315-162X PMID: 12913930 Document Number: 556558
Objective: Intramuscular gold is a well documented treatment in rheumatoid arthritis (RA), but its mechanism of action is still poorly understood. From an observation that gold sodium thiomalate (GSTM) induces monocyte-derived interleukin 6 (IL-6) and IL-10 production in vitro, a hypothesis has been proposed that gold exerts its action mainly as a selective immunostimulator rather than as a general immunosuppressant. In this prospective study we investigated cytokine production in peripheral blood from patients with RA during treatment with GSTM. Methods: A total of 20 patients with RA were treated with GSTM for at least 3 months. Disease activity was recorded at baseline, 12, 20, and 28 weeks. The ELISPOT method was used to measure spontaneous production of IL-6, IL-10, and interferon-gamma (IFN-gamma) from peripheral blood mononuclear cells (PBMC) at baseline and 4 and 12 weeks and production after incubation with GSTM in vitro, at different concentrations (0, 3, 12.5, 40 mug/ml) at baseline. IL-6 and IL-10 concentrations in serum were measured with ELISA. Results: The numbers of IL-10-producing cells were increased after 4 weeks' treatment with GSTM (p<0.01). The numbers of cells spontaneously producing IL-6 were increased after 4 weeks (p<0.01) and 12 weeks (p<0.01). The numbers of IFN-gamma-producing cells were increased after 4 weeks (p<0.01). Serum concentrations of IL-10 were increased after 4 weeks (p<0.01). Serum concentrations of IL-6 were not changed at any timepoint. The in vitro effect of GSTM on IL-10 production from PBMC at baseline predicted development of skin reactions during GSTM treatment, with lack of skin reactions being associated with high gold induced IL-10 production (p<0.05). There was no correlation between clinical response and cytokine production. Conclusion: This study indicates an immunostimulatory effect of GSTM treatment in patients with RA. The increase in IL-10 production during GSTM treatment may contribute to the positive effects of gold in RA.