title: Evidence for immunostimulatory effects of intramuscular gold in patients with rheumatoid arthritis: correlation with skin reactions.
abstract: 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-g (IFN-g) 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 micro g/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-g-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Rheumatology, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden. sofia.ernestam@hs.se
authors.forename: Sofia
authors.initials: S
authors.lastname: Ernestam
authors.forename: Jon
authors.initials: J
authors.lastname: Lampa
authors.forename: Siv
authors.initials: S
authors.lastname: Rogberg
authors.forename: Johan
authors.initials: J
authors.lastname: Rönnelid
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Ingiäld
authors.initials: I
authors.lastname: Hafström
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D006052:Gold Sodium Thiomalate / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012871:Skin Diseases / Q000276:immunology*
chemical_list: D018501:Antirheumatic Agents; D015850:Interleukin-6; D006052:Gold Sodium Thiomalate; D016753:Interleukin-10; D007371:Interferon-gamma