EFFECTS OF ROXITHROMYCIN ON PROLIFERATION OF PERIPHERAL-BLOOD MONONUCLEAR-CELLS AND PRODUCTION OF LIPOPOLYSACCHARIDE-INDUCED CYTOKINES

Roxithromycin (RXM), a new macrolide antibiotic, has a 14-member macro cycline ring structure which is similar to that of erythromycin. We in vestigated the effects of RXM on the proliferation of peripheral blood mononuclear cells (PBMCs) and the production of interleukin 1 beta (I L-1 beta) and tumor necrosis factor alpha (TNF-alpha) by PBMCs stimula ted with lipopolysaccharide (LPS). At concentrations greater than 25.0 mu g/ml, RXM suppressed the proliferation of PBMCs stimulated with ph ytohemagglutinin, probably due to cytotoxicity. When the PBMCs were in cubated with RXM for 7 d, the number of adherent cells (monocyte/macro phages) increased. Incubation with RXM at a concentration of 25.0 mu g /ml induced the greatest increase (p < 0.05). IL-1 beta and TNF-alpha were present 3 h after LPS-stimulation, and IL-1 beta production reach ed a peak at 12 h and TNF-alpha production at between 6 and 12 h, and then their production declined. RXM (25 mu g/ml) suppressed the produc tion of IL-1 beta and TNF-alpha slightly during the entire course of t he incubation. This suppression was dose-dependent. Anti-human granulo cyte-macrophage colony-stimulating factor and anti-human macrophage co lony stimulating factor antibodies had no effect on the RXM-induced pr oliferation of adherent cells. Suppression of the production of IL-1 b eta and TNF-alpha by RXM suggested that this drug might have anti-infl ammatory and immunosuppressive effects.