Anti-Inflammatory Effects of Besifloxacin, a Novel Fluoroquinolone, in Primary Human Corneal Epithelial Cells

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-1ss (IL-1ss), and Luminex technology was used to determine the effect of besifloxacin on IL-1ss-induced cytokine release. Effect of besifloxacin on nuclear factor kappa B (NFB), and mitogen-activated protein kinase (MAPK) was assessed by measuring inhibitory kappa B protein (IB) degradation, NFB 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-1ss increased release of 12 of the 29 cytokines measured. Besifloxacin significantly inhibited IL-1ss-induced cytokine release in a dose-dependent manner, with a comparable (IL-8) or better (G-CSF, GM-CSF, IL-6, MCP-1, MIP-1ss, TGF-, and TNF-) efficacy compared to moxifloxacin. A significant inhibitory effect of besifloxacin was observed at 1 or 10 g/ml. Besifloxacin inhibited IB degradation, NFB 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 NFB 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.