Stimulatory effects of anti-rheumatic drugs on human neutrophil functions.
Auranofin (AF), D-penicillamine (D-pen) and thiola are prescribed as disease-modifying drugs in the treatment of rheumatoid arthritis (RA). We have shown here that auranofin, 10(-8) to 10(-6) M, D-penicillamine, 10(-6) to 10(-3) M, thiola, 10(-7) to 10(-3) M, and the tripeptide thiol, glutathione, 10(-6) to 10(-3) M, enhanced f-met-leu-phe-induced lysosomal enzyme release and the phagocytic uptake of bacteria by up to 40%. The previously reported inhibitory effects of AF were only observed at concentrations in excess of those likely to be available to effector cells in vivo. The stimulatory effects of thiola and D-pen occurred at concentrations likely to be available to effector cells in vivo and, therefore, may be of greater clinical relevance. There is evidence that the drugs used in this study exert their effects via a thiol moiety and their therapeutic effect is preceded by an elevation of intracellular thiol levels.
Oben
J A
JA
Department of Pharmacology, University College London, U.K.
Foreman
J C
JC
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001310:Auranofin / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate; D005452:Fluoresceins; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008837:Micrococcus / Q000276:immunology; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010396:Penicillamine / Q000494:pharmacology; D010587:Phagocytosis; D013861:Thiocyanates; D008625:Tiopronin / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D005452:Fluoresceins; D013861:Thiocyanates; D001310:Auranofin; D008625:Tiopronin; D007770:L-Lactate Dehydrogenase; D009113:Muramidase; D005966:Glucuronidase; D010396:Penicillamine; D016650:Fluorescein-5-isothiocyanate