Effects of telithromycin in in vitro and in vivo models of lipopolysaccharide-induced airway inflammation

Chest. 2008 Jul;134(1):20-9. doi: 10.1378/chest.07-3056. Epub 2008 Apr 10.


Background: The ketolide antibiotic telithromycin (TEL) exerts immunomodulatory and antiinflammatory effects in vitro and in a mouse model of septic shock. We studied the antiinflammatory activity of TEL in in vitro and in vivo models of airway inflammation induced by lipopolysaccharide (LPS).

Methods: We measured the effects of TEL on the response of RAW 264.7 macrophages to LPS and of murine lung epithelial (MLE)-12 cells to supernatants of LPS-stimulated RAW 264.7 macrophages. Macrophage inflammatory protein (MIP)-2 and tumor necrosis factor (TNF)-alpha production, nuclear factor (NF)-kappaB activation, and apoptosis were determined. Acute airway inflammation was induced in untreated and TEL-treated BALB/c mice by nebulization with LPS. Total number of leukocytes, macrophages, and neutrophils, the protein concentration, and nitrite and cytokine levels were determined in the BAL fluid.

Results: TEL inhibited in a dose-dependent manner the production of MIP-2 and TNF-alpha by LPS-stimulated RAW 264.7 macrophages, and the production of MIP-2 by MLE-12 epithelial cells to supernatants of LPS-stimulated RAW 264.7 macrophages. NF-kappaB activation was inhibited and apoptosis was increased in both cell lines by TEL. The LPS-induced influx of neutrophils in BAL fluid was decreased by TEL pretreatment. TEL also reduced protein, nitrite, MIP-2, and TNF-alpha levels in the BAL fluid of LPS-nebulized animals.

Conclusions: We have provided evidence that TEL exerts potent antiinflammatory effects in LPS-induced airways injury. We propose that TEL acts in the early phase of inflammation by reducing the release of inflammatory mediators through NF-kappaB inhibition, and in the later phase through enhancement of inflammatory cell apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Apoptosis / drug effects
  • Bronchoalveolar Lavage Fluid
  • Cell Line
  • Cells, Cultured
  • Chemokine CXCL2 / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Ketolides / pharmacology*
  • Lipopolysaccharides
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism
  • Pneumonia / chemically induced
  • Pneumonia / metabolism
  • Pneumonia / pathology*
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Anti-Bacterial Agents
  • Chemokine CXCL2
  • Cxcl2 protein, mouse
  • Ketolides
  • Lipopolysaccharides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • telithromycin