In vivo efficacy of telithromycin on cytokine and nitric oxide formation in lipopolysaccharide-induced acute systemic inflammation in mice

J Antimicrob Chemother. 2006 Sep;58(3):615-21. doi: 10.1093/jac/dkl270. Epub 2006 Jul 19.


Objectives: The ketolide telithromycin represents a new subclass of 14-membered semisynthetic macrolides. Because there is evidence that traditional macrolides such as roxithromycin exert anti-inflammatory activity, we investigated the anti-inflammatory action of telithromycin against lipopolysaccharide (LPS)-induced acute systemic inflammation in mice in comparison with roxithromycin.

Methods: CD-1 mice were injected intraperitoneally with LPS (1 mg/kg), and the effects of pretreatment with a single intraperitoneal dose of telithromycin (150 mg/kg) or roxithromycin (50 mg/kg) for 2 h on the expression and formation of tumour necrosis factor alpha (TNFalpha), interleukin-1 beta (IL-1beta), interferon gamma (IFNgamma) and inducible nitric oxide synthase (NOS-II) as well as nitric oxide (NO) were analysed at different time points after LPS-treatment. Cytokine and NOS-II mRNA abundance was examined using real-time RT-PCR. Tissue cytokine levels were determined by enzyme-linked immunosorbent assay kits (ELISA); NO levels were measured by colorimetric assay kits.

Results: Pretreatment of mice with telithromycin as well as roxithromycin similarly attenuated the LPS-induced expression and formation of TNFalpha, IL-1beta and IFNgamma. Furthermore, the LPS-induced increase of NOS-II mRNA and the formation of NO were clearly diminished.

Conclusion: These results suggest that the ketolide telithromycin has anti-inflammatory properties like conventional macrolides due to inhibition of the production of proinflammatory cytokines, which leads to a decreased formation of NO in LPS-treated mice. Our data indicate that ketolides may have beneficial therapeutic effects independent of their antibacterial activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Cytokines / biosynthesis*
  • Cytokines / immunology
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Ketolides / therapeutic use*
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred Strains
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide / immunology
  • Organ Specificity
  • Roxithromycin / therapeutic use
  • Systemic Inflammatory Response Syndrome / chemically induced
  • Systemic Inflammatory Response Syndrome / drug therapy*
  • Systemic Inflammatory Response Syndrome / metabolism
  • Time Factors


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Ketolides
  • Lipopolysaccharides
  • lipopolysaccharide, Escherichia coli O111 B4
  • Roxithromycin
  • Nitric Oxide
  • telithromycin