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 macrocycline ring structure which is similar to that of erythromycin. We investigated the effects of RXM on the proliferation of peripheral blood mononuclear cells (PBMCs) and the production of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) by PBMCs stimulated with lipopolysaccharide (LPS). At concentrations greater than 25.0 μg/ml, RXM suppressed the proliferation of PBMCs stimulated with phytohemagglutinin, probably due to cytotoxicity. When the PBMCs were incubated with RXM for 7d, the number of adherent cells (monocyte/macrophages) increased. Incubation with RXM at a concentration of 25.0 μg/ml induced the greatest increase (p<0.05). IL-1β and TNF-α were present 3 h after LPS-stimulation, and IL-1β production reached a peak at 12 h and TNF-α production at between 6 and 12 h, and then their production declined. RXM (25 μg/ml) suppressed the production of IL-1β and TNF-α slightly during the entire course of the incubation. This suppression was dose-dependent. Anti-human granulocyte-macrophage colony-stimulating factor and anti-human macrophage colony stimulating factor antibodies had no effect on the RXM-induced proliferation of adherent cells. Suppression of the production of IL-1β and TNF-α by RXM suggested that this drug might have anti-inflammatory and immunosuppressive effects.