Experiments have been conducted to investigate a possible mechanism which might explain why
aurothiomalate (Autm), a
gold complex used in the treatment of
rheumatoid arthritis, is active in vivo but not in vitro, by testing the hypothesis that Autm is converted to
aurocyanide by activated polymorphonuclear leukocytes (PMN) which generate
cyanide from
thiocyanate, an
anion which is present in plasma at concentrations ranging from 20 to 200 microM. Two-stage experiments were conducted in which PMN, in the first stage, were activated by opsonized
zymosan in the presence of Autm both with and without
thiocyanate. Then, in the second stage, the effect of the drugs on
superoxide (O2-) production stimulated by a further addition of
zymosan was measured. Autm at concentrations of 10 and 100 microM decreased O2- production if
thiocyanate was present, but not if it was absent. By contrast, preformed
aurocyanide at 10 and 100 microM decreases O2- production by PMN stimulated by opsonized
zymosan both in the presence and absence of
thiocyanate. Changes in the ultraviolet spectra of the supernatants of PMN indicated that
aurocyanide was formed by activated PMN in the presence of
thiocyanate but not in its absence.