Modification of phagocytosis and cytokine production in peritoneal and splenic murine cells by erythromycin A, azithromycin and josamycin

Objectives: The aim of this study was to determine whether pre-incubation of peritoneal or splenic cells with different doses of the macrolides erythromycin A (14-membered ring), azithromycin (15-membered ring) and josamycin (16-membered ring) affects their phagocytic activity or cytokine production. Methods: Peritoneal and splenic cells from BALB/c mice were pre-incubated with different concentrations of these antibiotics, those similar to serum levels attained with the treatment schedules used in human therapy. Results: From our observations of phagocytic activity and IL-12 production by peritoneal cells, these macrolide antibiotics seem to act mainly as immunosuppressive agents, although they induce peritoneal cells to increase IL-18 production and splenic cells IL-4 production. Conclusions: Macrolide antibiotics can interfere with the Th1 cell-amplifying activity of IL-18 in conjunction with IL-12 and, in contrast, may induce a Th2 cell response in an IL-4-dependent manner. These results could improve their therapeutic use especially in immunosuppressed patients.