Studies of the effect of D-penicillamine and sodium aurothiomalate therapy on superoxide anion production by monocytes from patients with rheumatoid arthritis: evidence for in vivo stimulation of monocytes.

Abstract

SUMMARY The capacity of monocytes from patients with rheumatoid arthritis to generate superoxide anion in vitro after stimulation with serum treated zymosan (STZ) or IgG treated zymosan (IgTZ) was studied before and during therapy with penicillamine (n=9) or sodium aurothiomalate (AuTM) (n=12). Significant increases in rates of STZ (p<0-01) and IgTZ (p<002) stimulated superoxide anion production were seen after successful therapy (14 patients), which were paralleled by a significant increase in serum thiol levels. Patients who did not respond clinically to therapy (n=4) showed a smaller mean increase in serum thiol levels and had high mean rates of in vitro superoxide production before and after second-line therapy. Three patients were withdrawn from the study. The data suggest that successful therapy with penicillamine or AuTM may be associated with monocyte activation, and possible mechanisms are discussed.

D‐penicillamine and D‐penicillamine‐protein disulphide in plasma and synovial fluid of patients with rheumatoid arthritis.

“…D-pen-protein conjugates have been demonstrated on the surfaces of monocytes and macrophages incubated in vitro with D-pen-alb and D-pen, respectively (Binderup & Arrigoni-Martelli, 1979;Watanabe et al, 1986). They may be responsible for the alterations in monocyte behaviour seen in D-pen-treated rheumatoid arthritis patients (Hurst et al, 1986;McKeown et al, 1984). D-pen-alb or other D-pen-protein conjugates may therefore contribute to the antirheumatic action of D-pen.…”

Recent Advances of Gold Compounds in Anticancer Immunity

“…RAW 264.7, THP-1 cells Parente et al, 1989;Zetterstrom et al, 2008 AuTM Activates monocytes and enhances release of superoxide Human monocytes Hurst et al, 1986 Inhibits CD45 Wang et al, 1997 Na insertion, covalent binding, and even unobserved ways of acting, generate a number of damaged DNA cells and even induce the DNA mutation when the self-repair mechanisms dysfunction, thus exposing more neoantigens. According to a research by Kazuo and his co-workers, pretreatment with Au(III) complex of a model protein antigen (bovine ribonuclease A) induced novel antigen peptide recognized by CD4 + T cells (Takahashi et al, 1994) (Table 2).…”

Enhancement of Protein Kinase C-mediated EGF Receptor Phosphorylation by Auranofin

“…Thus, depending on the cell type and concentration of auranofin, inhibition or enhancement of cellular function may be found (3, 16). Nonetheless, a direct or indirect stimulatory effect of auranofin on PKC activity may be relevant to its antirheumatic effects and may well be the basis for the observation that gold therapy enhances monocyte and lymphocyte functions in rheumatoid arthritis (18,19).…”