Effect of roxithromycin on IL-8 synthesis and proliferation of nasal polypfibroblasts

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.