JAC Advance Access originally published online on July 19, 2006
Journal of Antimicrobial Chemotherapy 2006 58(3):615-621; doi:10.1093/jac/dkl270
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In vivo efficacy of telithromycin on cytokine and nitric oxide formation in lipopolysaccharide-induced acute systemic inflammation in mice
1 Department of Pharmacology und Toxicology, University of Regensburg Universitätsstr. 31, 93040 Regensburg, Germany 2 Department of Anesthesiology, University of Regensburg Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
Received 23 December 2005; returned 4 May 2006; revised 17 May 2006; accepted 2 June 2006
*Corresponding author. Tel: +49-941-9434780; Fax: +49-941-9434772; E-mail: kristina.lotter{at}chemie.uni-regensburg.de
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 (TNF
), interleukin-1 beta (IL-1ß), interferon gamma (IFN
) 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 TNF, IL-1ß and IFN. 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.
Keywords: telithromycin , lipopolysaccharide , tumour necrosis factor alpha , interleukin-1 beta , interferon gamma , nitric oxide
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