T. Yoshimura et al., EFFECTS OF ROXITHROMYCIN ON PROLIFERATION OF PERIPHERAL-BLOOD MONONUCLEAR-CELLS AND PRODUCTION OF LIPOPOLYSACCHARIDE-INDUCED CYTOKINES, Biological & pharmaceutical bulletin, 18(6), 1995, pp. 876-881
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.