Changes in immune function in patients with rheumatoid arthritis following treatment with sodium aurothiomalate.

Abstract

SUMMARY The mitogenic response of peripheral blood lymphocytes from21 patients with rheumatoid arthritis to concanavalin-A (con-A), phytohaemagglutinin (PHA), and pokeweed mitogen (PWM) was significantly lower than in 30 normal subjects. After 15-24 weeks' treatment with sodium aurothiomalate (GST) the response to these mitogens rose to within the normal range. Improvement over pretreatment values was significant for con-A and PWM measured as area under the dose response curve but only for con-A if response at optimal mitogen concentration is the sole criterion. The improvement in PHA response was not significant with either method of measurement. There was an improvement in disease activity by 15-24 weeks as measured by a fall in serum C-reactive protein (CRP), IgM rheumatoid factor (RF), Clq binding activity (C1qBA), and Ritchie articular index. Con-A lymphocyte responsiveness was inversely related to serum CRP levels, but measurements of disease activity were otherwise unrelated to lymphocyte mitogen responsiveness. The observed improvement in peripheral blood lymphocyte responsiveness during gold treatment contrasts with the suppressive effect of gold in vitro. We suggest that the improvement in lymphocyte function is due to the lessening of rheumatoid disease activity during gold treatment, and that the low serum gold levels in our patients were insufficient to mask this effect. Sera from some of our patients were capable of suppressing the function of normal lymphocyfes, and this was less apparent after treatment. The suppressive effect of sera correlated with ClqBA. Suppressive factors in serum, including possibly immune complexes, may be one factor leading to suppression of lymphocyte function during rheumatoid arthritis. Such an inverse relationship between humoral and cellular immune mechanisms might influence the clinical expression of rheumatoid arthritis.Gold salts have been shown in controlled trials to be most apparent with gold concentrations of 10-100 effective in the treatment of rheumatoid arthritis.1-3 ,tg/ml and has been shown to be due to an effect on However, the means by which gold inhibits inflam-monocytes. Rosenberg and Lipsky1" have also mation in rheumatoid arthritis is unknown, although shown that gold can inhibit pokeweed mitogen a wide variety of mechanisms have been investi-induced immunoglobulin production by human gated.4 As immunological processes, and especially lymphocytes. Gold has an inhibitory effect on the the function of lymphocytes,5 are thought to be mixed leucocyte reaction7 91012 and cell-mediated important in the pathogenesis of the disease, the cytotoxicity9 12 13 when present at the initiation of effects of gold on immune mechanisms have been culture.9 13 Thus, there is evidence from in-vitro studied.experiments with human peripheral blood mono-A number of studies6-10 have shown that gold nuclear cells that gold inhibits several lymphocyte present at the initiation of lymphocyte cultures in functions, possibly due to its effect on monocytes. vitro suppresses lymph...

Analysis of the antigen specific helper T cell function and HLA‐DR of Israeli patients with rheumatoid arthritis (RA)

“…Drug treatment, especially with gold and penicillamine, has been shown to affect non-specific immune functions in patients with RA (Highton et al 1981, Percy et al 1978. Our results ( Table 1) indicate that these drugs indeed affect the immune response potential.…”

Enhancement of Antibody Production by Mercury and Platinum Group Metal Halide Salts

“…In vitro culture systems with peripheral mononuclear cells (PMN) stimulated with pokeweed mitogen (PWM) in the presence or absence of sodium aurothiomalate showed increased 3H-thymidine up take when PMN and gold were mixed together, with gold having no effect per se [20,21]. The postulated mode of action of this compound, and possibly the platinum salts, is highly dose-dependent in that acti vation of macrophages by the injection of these com pounds leads to release of interleukin 1 (IL-1), which has a dual action on T and B cells.…”

The effect of gold treatment on monocyte interleukin-1 production in rheumatoid arthritis

“…Gold compounds have previously been shown to correct abnormalities in circulating lymphocyte function in RA patients both in vitro [12] and in vivo [13]. Gold also has the potential to inhibit monocyte IL-I production in vitro [14][15][16].…”