Aryl-fluoroquinolone derivatives A-56619 (difloxacin) and A-56620 inhibit mitogen-induced human mononuclear cell proliferation

Abstract

Aryl-fluoroquinolone derivatives A-56619 (difloxacin) and A-56620 were found to inhibit human peripheral blood mononuclear cell (MNC) proliferation (measured by [3H]thymidine uptake) that was induced by concanavalin A or monoclonal antibody OKT3. These antimicrobial agents exert their maximum suppressive effect when added within the first 24 h after the onset of culture with concanavalin A. No increase in the concentration of mitogen or the duration of incubation of MNC cultures reversed this inhibitory effect, but the removal of the drug from cultures reversed the suppression of DNA synthesis. A-56619 appeared not to interfere with the triggering of MNC activation by mitogen because it did not inhibit mitogen-induced increase in protein synthesis (measured by [3H]leucine incorporation), interleukin-2 receptor expression (measured by the binding of fluorescein-conjugated monoclonal antibody against interleukin-2 receptor), and cell volume. These findings are considered in terms of possible interference of aryl-fluoroquinolones with mammalian topoisomerase and DNA polymerases.