Alterations of host response by a long-term treatment of roxithromycin

Roxithromycin (10 mg/kg) was administered once-daily for seven or 28 days to mice intragastrically and its effects on cytokine synthesis were studied. Administration of roxithromycin for 28 days resulted in increased synthesis of interleukin (IL)-1 and tumour necrosis factor (TNF-alpha) production by macrophages, and the production of IL-2, IL-4 and interferon gamma by splenocytes. In contrast, 7 day administration of roxithromycin did not affect these parameters. Furthermore, clindamycin treatment did not significantly increase the capacity of host cells to produce cytokines, irrespective of the duration of treatment, when compared with the solvent control receiving 0.9% ethanol solution or the untreated controls. In addition, the supernatant of a 7 day culture of splenocytes with roxithromycin showed suppression of the production of TNF-alpha and prostaglandin E2 by mitogen-stimulated macrophages, and this suppressive activity was impaired by a monoclonal antibody to murine IL-4. Thus, this data suggests that roxithromycin may not only enhance the host defence system through increased cytokine synthesis by host cells, but also exhibit anti-inflammatory activity by including an anti-inflammatory cytokine, IL-4.