Gold and penicillamine: a proposed mode of action in rheumatoid arthritis, based on synovial fluid analysis.

Abstract

SUMMARY Although in common use, there is still controversy as to the way in which gold and penicillamine act in rheumatoid arthritis (RA).In this study, synovial fluids from 4 groups of patients have been compared: (1) RA patients on gold/penicillamine, (2) RA patients on non-steriodal anti-inflammatory drugs (NSAID) only, (3) osteoarthritis patients, and (4) patients with sero-negative arthropathies. The parameters measured were differential agglutination titre (DAT), total haemolytic complement (CH50), total protein, total white cell count, and immunoglobulins. RA patients on gold/penicillamine have lower synovial DAT levels and higher CH50 levels than RA patients on NSAID only, and total and cryoprecipitable IgM levels very close to those found in the sero-negative joint fluids. The non-specific inflammatory parameters, ie, white cell count and total protein are unchanged after gold/penicillamine therapy.In a second study, the serum DATs of patients in total remission after gold/penicillamine were compared with similar patients on NSAID only. The DAT falls significantly in the former group (P<0 *001), but not in the latter suggesting that fall in DAT is a consequence of therapy rather than remission.The parameters altered by gold/penicillamine in the synovial fluid are those that distinguish RA from non-rheumatoid arthropathies suggesting the drug's primary effect is to render the disease sero-negative. The results support the hypothesis that both drugs have a common mode of action based on their active thiol groups, and that the fall in DAT is due to the reduAtion of the antigenicity of the IgG complexes.

Effects of gold therapy on the synthesis and quantity of serum and synovial fluid IgM, IgG, and IgA rheumatoid factors in rheumatoid arthritis patients

“…Their exact mechanism in disease modulation is unclear. Serum immunoglobulin and IgM-RF levels are known to decrease with gold therapy (25)(26)(27); however, the effect of gold salts on other serum RFs, in particular IgG-RF, is unknown. Furthermore, gold therapy-related changes in synovia1 fluid (SF) RF levels and in RF production by synovial membrane (SM) (which are of greater relevance because of their proximity to the site of articular damage) have not been fully documented.…”

Immunological Effects of Biarison® in the Treatment of Rheumatoid Arthritis and Systemic Lupus Erythematosus:A Preliminary Report

“…D-Peniciilamine dissociates macroglobulins, resulting in a fall in R F titres (7). A decrease in immunoglobulin levels is also seen in patients on long-term D-penicillamine therapy (12). The therapeutic value of these basic anti-rheumatic agents is thought to correlate with the observed decrease in abnormal immunoglobulins and R F titres.…”

“…In long-term treatment with gold salts, a decrease is seen in the serum levels as well as in the synovial fluid levels of immunoglobulins and rheumatoid factor (RF) titres in patients with RA (12). D-Peniciilamine dissociates macroglobulins, resulting in a fall in R F titres (7).…”