Besifloxacin, a novel fluoroquinolone antimicrobial agent, exhibits potent inhibition of pro-inflammatory cytokines in human THP-1 monocytes.
OBJECTIVE
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)-1beta, IL-8, interferon-inducible protein (IP-10), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha)] or better [granulocyte CSF (G-CSF), IL-1alpha, 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-1alpha, at 1 mg/L for G-CSF, IL-1ra and IL-6 and at 30 mg/L for GM-CSF, IL-12p40, IL-1beta, IL-8, IP-10, MCP-1 and MIP-1alpha.


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.
Zhang
Jin-Zhong
JZ
Global Preclinical Development, Bausch & Lomb, 1400 North Goodman Street, Rochester, NY 14603, USA. jinzhong.zhang@bausch.com
Ward
Keith W
KW
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001381:Azepines / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors*; D015817:Eye Infections / Q000188:drug therapy; D024841:Fluoroquinolones / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D015394:Molecular Structure; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001381:Azepines; D016207:Cytokines; D024841:Fluoroquinolones; D008070:Lipopolysaccharides; C522124:besifloxacin