Although several studies have demonstrated that low-dose, long-term 14-memb
er macrolides (erythromycin (EM), roxithromycin (RXM), clarithromycin (CAM)
) are effective in the treatment of chronic airway diseases like chronic si
nusitis and diffuse panbronchiolitis (DPB), the mechanism of action of thes
e drugs is not yet clear. Both these airway diseases are associated with an
increase in the proliferation of fibroblasts. Moreover, fibroblasts are al
so an important source of proinflammatory cytokines such as interleukin-8 (
IL-8), that play an important role in the pathogenesis of nasal polyps. The
refore, using primary fibroblast lines derived from nasal polyps, we invest
igated the effect of RXM on the synthesis of IL-8 and proliferation of nasa
l polyp fibroblasts (NPF). These fibroblasts were either treated with lipop
olysaccharide (LPS) and RXM for 24 h, or pre-incubated with RXM for 24 h an
d then treated with LPS and RXM for 24 h. The level of IL-8 mRNA in NPF was
analysed by reverse transcriptase-polymerase chain (RT-PCR) and the level
of IL-8 in culture supernatants was measured by ELISA. Next, the proliferat
ive capacity of NPF after treatment with RXM was analysed by cell counting
and H-3-thymidine uptake. RXM had no effect on LPS-induced IL-8 synthesis b
y NPF. On the other hand, RXM suppressed the proliferation of NPF in a dose
-dependent manner. These findings suggest that, although RXM cannot directl
y inhibit the synthesis of IL-8, it probably reduces IL-8 production by inh
ibiting the proliferation of NPF.