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JAC Advance Access originally published online on October 25, 2007
Journal of Antimicrobial Chemotherapy 2008 61(1):111-116; doi:10.1093/jac/dkm398
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Besifloxacin, a novel fluoroquinolone antimicrobial agent, exhibits potent inhibition of pro-inflammatory cytokines in human THP-1 monocytes

Jin-Zhong Zhang* and Keith W. Ward

Global Preclinical Development, Bausch & Lomb, 1400 North Goodman Street, Rochester, NY 14603, USA

Received 25 June 2007; returned 10 August 2007; revised 20 August 2007; accepted 23 September 2007

* Corresponding author. Tel: +1-585-338-6238; Fax: +1-585-338-6223; E-mail: jinzhong.zhang{at}bausch.com

Objectives: This study was conducted to evaluate the anti-inflammatory effects of besifloxacin, a novel fluoroquinolone under clinical evaluation for treatment of ophthalmic infections.

Methods: Cytokine expression in human THP-1 monocytes was stimulated by lipopolysaccharide (LPS), and Luminex technology was used to determine the effect of besifloxacin on LPS-induced cytokine expression. Moxifloxacin, a marketed fluoroquinolone used in ophthalmic infections, was used as the control.

Results: LPS induced measurable cytokine expression for 14 of the 16 cytokines assayed. Besifloxacin significantly inhibited LPS-stimulated cytokine production in a dose-dependent manner, with a comparable [granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1β, IL-8, interferon-inducible protein (IP-10), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1{alpha} (MIP-1{alpha})] or better [granulocyte CSF (G-CSF), IL-1{alpha}, IL-1 receptor antagonist (IL-1ra) and IL-6] potency compared with moxifloxacin. A significant inhibitory effect of besifloxacin was observed at 0.1 mg/L for IL-1{alpha}, at 1 mg/L for G-CSF, IL-1ra and IL-6 and at 30 mg/L for GM-CSF, IL-12p40, IL-1β, IL-8, IP-10, MCP-1 and MIP-1{alpha}.

Conclusions: Besifloxacin acts as an anti-inflammatory agent in monocytes in vitro; this attribute may enhance its efficacy in ocular infections with an inflammatory component and warrants further investigation.

Keywords: antibiotics , lipopolysaccharide , moxifloxacin , ophthalmic infections , Luminex


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