Suppressive activity of a macrolide antibiotic, roxithromycin, on pro-inflammatory cytokine production in vitro and in vivo

THIS study was designed to examine the influence of a macrolide antibiotic, roxithromycin (RXM), on the production of pro-inflammatory cytokines, inte rleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha. In. the first ex periments, we examined the effect of RXM on in vitro cytokine production fr om lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes. Th e monocytes were cultured in the presence of various doses of the agent. Af ter 24 h, the culture supernatants were obtained and assayed for IL-1 beta and TNF-alpha contents by enzyme-linked immunosorbent assay. RXM suppressed the in vitro production of IL-1 beta and TNF-alpha in response to LPS stim ulation. This was dose dependent and first noted at a concentration of as l ittle as 0.05 mu g/ml, which is much lower than therapeutic blood levels. i n the second part of the experiments, we examined the influence of RXM on t he appearance of IL-1 beta and TNF-alpha in mouse lung extract induced by L PS inhalation, RXM was administered orally into BALB/c mice at a single dos e of 2.5 mg/kg once a day for 5-12 weeks. These mice were then instilled wi th LPS into the trachea and examined for the presence of cytokines in aqueo us lung extracts. Pretreatment of mice with RXM for 5 weeks did not influen ce of the appearance of both IL-1 beta and TNF-alpha in aqueous lung extrac ts. However, pretreatment for more than 7 weeks dramatically suppressed the cytokine appearance in the extracts.