Effect of auranofin, an antirheumatic drug, on neutrophil apoptosis

Objective: The effects of auranofin (AF) on apoptosis and on the biological functions of neutrophils were investigated. Methods. Neutrophils were incubated with various concentrations of AF for d ifferent periods. Cell viability was determined by the MTS assay and apopto sis was evaluated by flow cytometric analysis of propidium iodide (PI)- sta ining of the nuclei and annexin-V staining of phosphatidylserine in the cel l membrane. The effect of AF on the expression of adhesion molecules (CD62L and CD11b/CD18) and on the generation of O-2(-) by neutrophils was also de termined. Results: At a low concentration (1 mu M), AF significantly prolonged neutro phil survival by delaying spontaneous apoptosis. Neutrophils incubated with AF for 12 and 24 hours maintained the capacity to express adhesion molecul es and generate O-2(-). In contrast, a higher AF concentration (5 mu M) sho rtened neutrophil survival by the induction of cell necrosis. Conclusion: Although the biological significance of inhibitory effect of AF on neutrophil apoptosis remains unclear, it seems to be unlikely that AF e xerts the anti-inflammatory effect in vivo by directly suppressing neutroph il functions. Since AF has a wide range of effects on leukocytes, its thera peutic benefit in rheumatoid arthritis may be mediated in a complex manner.