JAC Advance Access published online on July 19, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl270
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1 Department of Pharmacology und Toxicology, University of Regensburg, Universitätsstr. 31, 93040 Regensburg, Germany
* To whom correspondence should be addressed. 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 Results: Pretreatment of mice with telithromycin as well as roxithromycin similarly attenuated the LPS-induced expression and formation of TNF 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.
Received December 23, 2005
Revised May 17, 2006
Accepted June 2, 2006
Original article
In vivo efficacy of telithromycin on cytokine and nitric oxide formation in lipopolysaccharide-induced acute systemic inflammation in mice
Kristina Lotter 1 *, Klaus Höcherl 1, Michael Bucher 2, and Frieder Kees 1
2 Department of Anesthesiology, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
Kristina Lotter, E-mail: kristina.lotter{at}chemie.uni-regensburg.de
Abstract 
), interleukin-1 beta (IL-1
), 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., IL-1 and IFN. Furthermore, the LPS-induced increase of NOS-II mRNA and the formation of NO were clearly diminished.
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