Auranofin modulates mast cell histamine and polymorphonuclear leukocyte collagenase release

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Abstract
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.