Auranofin and its combination with LTB₄ influences ATP level and migration of human polymorphonuclear cells in vitro

Abstract

Auranofin (AF), an orally administered antirheumatic drug, reduces the ATP level of PMN cells in vitro in a dose-dependent manner and provokes various effects on PMN migration. Under the experimental conditions, AF in concentrations between 10⁻⁸ M and 10⁻³ M produced a statistically significant (P < 0.05) dose-related reduction in ATP level, which ranged from 89% of the control value with 10⁻⁸ M AF to 46.8% of the control with 10⁻³ M AF. On the other hand, the combination of AF and the chemoattractant LTB₄ (1 ng/ml) shows agonistic effects on the intracellular ATP level. AF at 10⁻⁵ M significantly increases the ATP (33%;P < 0.03). In general migration of PMN cells is stimulated by 10⁻⁷ M AF [chemotactic index (CI)=1.26], but inhibited by 10⁻⁵ M (CI=0.65), 10⁻⁴ M (CI=0.09) and 10⁻³ M AF (CI=0.01). These effects were statistically significant atP < 0.05. In the presence of LTB₄ (1 ng/ml), which resulted in an average CI of 2.9, AF also inhibits the chemotactic effect of the chemoattractant, with the CI being significantly reduced at 10⁻⁶ M AF (CI=2.3) and 10⁻⁴ M AF (CI=0.05). In the latter case the effect was also confirmed by the leading-front technique. AF at 10⁻⁶ M is a level that could be reached in the blood after continuous therapy regimens, and these results are therefore of practical interest. They expand our knowledge of the effects of AF on PMN cells, whereby reducing effects on intracellular ATP were observed with AF alone and stimulating effects in combination with LTB₄. With low AF concentrations, the reduction of the ATP level is only a part of its action that seems to be independent of its effect on cell migration and chemotaxis.