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SOFIA ERNESTAM, JON LAMPA, SIV ROGBERG, JOHAN RÖNNELID, LARS KLARESKOG, and INGIÄLD HAFSTRÖM

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 µg/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.

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. (J Rheumatol 2003;30:1748-55)

Key Indexing Terms:

GOLD
RHEUMATOID ARTHRITIS
INTERLEUKIN 10
INTERLEUKIN 6
INTERFERON-g
MONOCYTES

Supported by the Swedish Medical Research Council, the Swedish Association Against Rheumatism, Gustav V 80-Year Foundation, and the AFA Insurance Company.

S. Ernestam, MD, Department of Rheumatology, Huddinge University Hospital; J. Lampa, MD; S. Rogberg, MSc; L. Klareskog, MD, PhD, Rheumatology Unit, Karolinska Hospital; J. Rönnelid, MD, PhD, Rheumatology Unit, Karolinska Hospital, Department of Clinical Immunology, University Hospital, Uppsala; I. Hafström, MD, PhD, Department of Rheumatology, Huddinge University Hospital.

Dr. Ernestam and Dr. Lampa contributed equally to this work.

Address reprint requests to Dr. S. Ernestam, Department of Rheumatology, Huddinge University Hospital, SE-141 86 Stockholm, Sweden. E-mail: sofia.ernestam@hs.se

Submitted June 7, 2002; revision accepted January 16, 2003.