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

Mediators Inflamm. 1999;8(4-5):199-204. doi: 10.1080/09629359990351.


This study was designed to examine the influence of a macrolide antibiotic, roxithromycin (RXM), on the production of pro-inflammatory cytokines, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. In the first experiments, we examined the effect of RXM on in vitro cytokine production from lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes. The monocytes were cultured in the presence of various doses of the agent. After 24 h, the culture supernatants were obtained and assayed for IL-1beta and TNF-alpha contents by enzyme-linked immunosorbent assay. RXM suppressed the in vitro production of IL-1beta and TNF-alpha in response to LPS stimulation. This was dose dependent and first noted at a concentration of as little as 0.05 microg/ml, which is much lower than therapeutic blood levels. In the second part of the experiments, we examined the influence of RXM on the appearance of IL-1beta and TNF-alpha in mouse lung extract induced by LPS inhalation. RXM was administered orally into BALB/c mice at a single dose of 2.5 mg/kg once a day for 5-12 weeks. These mice were then instilled with LPS into the trachea and examined for the presence of cytokines in aqueous lung extracts. Pretreatment of mice with RXM for 5 weeks did not influence of the appearance of both IL-1beta and TNF-alpha in aqueous lung extracts. However, pretreatment for more than 7 weeks dramatically suppressed the cytokine appearance in the extracts.

MeSH terms

  • Administration, Inhalation
  • Administration, Oral
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Humans
  • Instillation, Drug
  • Interleukins / biosynthesis*
  • Interleukins / blood
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / pharmacology
  • Lung / drug effects*
  • Lung / physiology
  • Lymphocytes / drug effects*
  • Lymphocytes / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Roxithromycin / administration & dosage
  • Roxithromycin / pharmacology*
  • Trachea
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • Anti-Bacterial Agents
  • Cytokines
  • Interleukins
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Roxithromycin