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

Lotter, Kristina and Hoecherl, Klaus and Bucher, Michael and Kees, Frieder (2006) In vivo efficacy of telithromycin on cytokine and nitric oxide formation in lipopolysaccharide-induced acute systemic inflammation in mice. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 58 (3). pp. 615-621. ISSN 0305-7453, 1460-2091

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Abstract

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 alpha), interleukin-1 beta (IL-1 beta), interferon gamma (IFN gamma) 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 alpha, IL-1 beta and IFN gamma. 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.

Item Type: Article
Uncontrolled Keywords: NECROSIS-FACTOR-ALPHA; MACROLIDE ANTIBIOTICS; HUMAN MONOCYTES; SUPPRESSIVE ACTIVITY; KAPPA-B; EXPRESSION; ENDOTOXIN; SYNTHASE; CLARITHROMYCIN; ROXITHROMYCIN; telithromycin; lipopolysaccharide; tumour necrosis factor alpha; interleukin-1 beta; interferon gamma; nitric oxide
Subjects: 600 Technology > 610 Medical sciences Medicine
600 Technology > 615 Pharmacy
Divisions: Medicine > Lehrstuhl für Anästhesiologie
Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Prof. Frieder Kees
Depositing User: Dr. Gernot Deinzer
Date Deposited: 03 Feb 2021 06:08
Last Modified: 03 Feb 2021 06:08
URI: https://pred.uni-regensburg.de/id/eprint/34099

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