Fundamental research of the effect of a variety of chemotherapeutics on leukocyte functions

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Macrophages and neutrophils play an important role in natural host defense system. When these phagocytes recognize foreign particles, such as bacterium and fungi, they escape the vascular system, migrate towards the site of infection, followed by phagocytosis and intracellular killing of the invading microorganisms by bactericidal reactive oxygen species derived from the superoxide anion. To determine whether antimicrobials affect these functions, we examined the effect of 6 new quinolones, ofloxacin (OFLX), lomefloxacin (LFLX), tosufloxacin (FLRX), fleroxacin (FLRX), sparfloxacin (SPFX) and levofloxacin (LVFX) on the function of rat peripheral macrophages and neutrophils. In vitro treatment of the new quinolones was effective in markedly potentiating the production of superoxide anion in macrophages. The potentiation of the production of superoxide anion is prolonged with TFLX but transient for OFLX, LFLX, FLRX, SPFX and LVFX. In contrast, TFLX markedly potentiated adhesion in macroph … More ages. No significant alteration was detected in the adhesion in macrophages treated with the other new quinolones. In addition, all of the new quinolones significantly inhibited chemotaxis and phagocytosis of E. coli in macrophages. Moreover, OFLX, LFLX, TFLX, and LVFX were effective in significantly potentiating the production of hydrogen peroxide in macrophages, while the other agents did not affect that. By contrast, OFLX, LFLX, FLRX and LVFX caused an increase of phagocytosis of E. coli in neutrophils. However, TFLX and SPFX failed to significantly affect phagocytosis in neutrophils. Furthermore, LFLX and SPFX significantly potentiated adhesion of neutrophils. A potentiation by TFLX was seen with the production of superoxide anion in neutorphils, while the other five new quinolones were effective in markedly reducing that production in neutrophils. Moreover, TFLX was effective in significantly potentiating the production of hydrogen peroxide in neutrophils, whereas sparfloxacin markedly inhibited such production. Therefore, the new quinolones may differentially affect the function of macrophages and neutrophils. Less