Inhibition of IL-6 and IL-8 induction from cultured rheumatoid synovial fibroblasts by treatment with aurothioglucose

Gold compounds have long been used in the treatment of rheumatoid arthritis (RA). However, their actions in HA have not been clarified. In this study, we examined the effect of one of the monovalent gold compounds, aurothiogl ucose (AuTG), on the IL-1-induced production of IL-6, IL-8 and granulocyte macrophage colony stimulating factor (GM-CSF) from rheumatoid synovial fibr oblasts (RSF) isolated from three HA patients. IL-6 and IL-8 induction but not GM-CSF induction was inhibited in most of the RSF after pretreatment wi th AuTG. Since gene expression of these cytokines is known to be under the control of a common transcription factor, NF-kappa B, the effect of AuTG on the cellular localization of NF-kappa B (p65 subunit) and on NF-kappa B-DN A binding was examined. Although AuTG treatment did not prevent NF-kappa B nuclear translocation, AuTG blocked the DNA-binding activity of NF-kappa B when examined in vitro. Morphologically, both metal-specific cell staining using p-dimethylaminobenzylidene rhodamine and transmission electron micros copic examinations demonstrated the accumulation of metal gold in the cytop lama and some organella (mitochondria and lysosomes) of the AuTG-treated RS F, These results indicate that one of the anti-rheumatic actions of AuTG mi ght be through its inhibitory action on NF-kappa B.