Auranofin modulates mast cell histamine and polymorphonuclear leukocyte collagenase release.
Auranofin, an orally gold preparation, effective in the treatment of rheumatoid arthritis, was found to be a potent noncytotoxic inhibitor of histamine and collagenase release from mast cells and polymorphonuclear (PMN) leukocytes respectively. Histamine release has been inhibited by auranofin in dose-dependent fashion. Auranofin at concentration of 10(-5) M inhibited 100% of the release, lower concentration 10(-6) M and 10(-7) M produced 80 and 40% decrease. The exposure of PMN-leukocytes to auranofin caused also dose-dependent inhibition of collagenase release. Auranofin at a concentration of 10(-4) M produced a marked reduction (75-100%) of enzyme release from human and rat blood PMN-leukocytes. The modest inhibition 40 and 15-20% at a concentration of 10(-5) M and 10(-6) M respectively was obtained. Auranofin more significantly suppressed collagenase release from leukocytes isolated from inflammatory exudate. Decrease of 100, 80 and 60% were observed upon addition of 10(-4) M, 10(-5) M and 10(-6) M of auranofin. These results suggest that therapeutic action of auranofin may be caused, at least in part, by the inhibition of cellular release of histamine and collagenase in the course of inflammation.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001310:Auranofin; D006051:Aurothioglucose / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006046:Gold / Q000031:analogs & derivatives*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D003012:Microbial Collagenase / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D051381:Rats
D000893:Anti-Inflammatory Agents; D006051:Aurothioglucose; D001310:Auranofin; D006046:Gold; D003012:Microbial Collagenase