Anti-inflammatory effects of besifloxacin, a novel fluoroquinolone, in primary human corneal epithelial cells.

Abstract

PURPOSE:

The aim of this study was to determine the anti-inflammatory effects of besifloxacin, a novel fluoroquinolone under clinical evaluation for the treatment of ophthalmic infections, in human corneal epithelial cells (HCEpiC).

METHODS:

Cytokine expression in primary HCEpiC was stimulated by interleukin-1beta (IL-1beta), and Luminex technology was used to determine the effect of besifloxacin on IL-1beta-induced cytokine release. Effect of besifloxacin on nuclear factor kappa B (NFkappaB), and mitogen-activated protein kinase (MAPK) was assessed by measuring inhibitory kappa B protein (IkappaB) degradation, NFkappaB nuclear translocation, and MAPK phosphorylation by Western blotting. Moxifloxacin, a marketed fluoroquinolone, was used as the control. Anti-inflammatory efficacy of besifloxacin was also evaluated in rabbits infected with methicillin-resistant Staphylococcus aureus (MRSA).

RESULTS:

Stimulation of HCEpiC with IL-1beta increased release of 12 of the 29 cytokines measured. Besifloxacin significantly inhibited IL-1beta-induced cytokine release in a dose-dependent manner, with a comparable (IL-8) or better (G-CSF, GM-CSF, IL-6, MCP-1, MIP-1beta, TGF-alpha, and TNF-alpha) efficacy compared to moxifloxacin. A significant inhibitory effect of besifloxacin was observed at 1 or 10 microg/ml. Besifloxacin inhibited IkappaB degradation, NFkappaB nuclear translocation, and activation of p38 and JNK MAPKs. Based on improvement of clinical score, besifloxacin showed statistically significant anti-inflammatory effect compared to saline treatment.

CONCLUSIONS:

Besifloxacin acts as an anti-inflammatory agent in corneal epithelial cells in vitro, by inhibiting the NFkappaB and MAPK pathways. Besifloxacin also exhibits anti-inflammatory efficacy in vivo. The anti-inflammatory attribute may enhance its efficacy in the treatment of ocular infections with an inflammatory component and warrants further investigation.

• Authors: Jin-Zhong Zhang, Megan E Cavet, Keith W Ward
• Journal: Current eye research (Curr Eye Res) Vol. 33 Issue 11 Pg. 923-32 (Nov 2008) ISSN: 1460-2202 [Electronic] England
• PMID: 19085374 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Aza Compounds
• Azepines
• Cytokines
• Fluoroquinolones
• Interleukin-1beta
• NF-kappa B
• Quinolines
• besifloxacin
• Mitogen-Activated Protein Kinases
• Moxifloxacin

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage, pharmacology)
• Aza Compounds (pharmacology)
• Azepines (administration & dosage, pharmacology)
• Biological Transport (drug effects)
• Cell Nucleus (metabolism)
• Cells, Cultured
• Cytokines (antagonists & inhibitors, metabolism)
• Dose-Response Relationship, Drug
• Endophthalmitis (pathology)
• Enzyme Activation (drug effects)
• Epithelium, Corneal (cytology, drug effects)
• Female
• Fluoroquinolones (administration & dosage, pharmacology)
• Humans
• Interleukin-1beta (pharmacology)
• Mitogen-Activated Protein Kinases (metabolism)
• Moxifloxacin
• NF-kappa B (metabolism)
• Quinolines (pharmacology)
• Rabbits