Azithromycin and ciprofloxacin inhibit interleukin‐8 secretion without disrupting human sinonasal epithelial integrity in vitro. Issue 2 (28th July 2020)

• Record Type: Journal Article
• Authors: Lim, Dong‐Jin; Thompson, Harrison M.; Walz, Christopher R.; Ayinala, Samrath; Skinner, Daniel; Zhang, Shaoyan; Grayson, Jessica W.; Cho, Do‐Yeon; Woodworth, Bradford A.
• Is Part Of: International forum of allergy & rhinology. Volume 11:Issue 2(2021)
• Page Start: 136
• Page End: 143
• Publication Date: 2020-07-28
• Subjects: interleukin‐8 -- azithromycin -- ciprofloxacin -- sinus stents -- chronic rhinosinusitis -- sinusitis -- pseudomonas; 617.51005
• DOI: 10.1002/alr.22656
• Languages: English
• ISSNs: 2042-6976

Abstract

Abstract : Background: We recently developed a ciprofloxacin and azithromycin sinus stent (CASS) to target recalcitrant infections in chronic rhinosinusitis (CRS). The objective of this study was to evaluate the anti‐inflammatory activity of azithromycin released from the CASS and assess the impact on the integrity and function of primary human sinonasal epithelial cells (HSNECs). Methods: Pseudomonas aeruginosa lipopolysaccharide (LPS)‐stimulated HSNECs were treated with azithromycin and/or ciprofloxacin at concentrations attainable from CASS release. Interleukin‐8 (IL‐8) secretion was quantified by enzyme‐linked immunosorbent assay (ELISA). Epithelial integrity (transepithelial resistance [TEER], paracellular permeability [fluorescein isothiocyanate‐labeled dextran], lactate dehydrogenase [LDH] assays) and function (ciliary beat frequency [CBF]) were also evaluated. Results: Azithromycin significantly reduced secreted IL‐8 from P. aeruginosa LPS‐stimulated HSNECs at all concentrations tested (mean ± standard deviation; control = 5.77 ± 0.39 ng/mL, azithromycin [6 μg/mL] = 4.58 ± 0.40 ng/mL, azithromycin [60 µg/mL] = 4.31 ± 0.06, azithromycin [180 µg/mL] = 4.27 ± 0.26 ng/mL, p < 0.05). Co‐incubation with azithromycin (6 µg/mL) and ciprofloxacin (2.4 µg/mL) in LPS‐stimulated HSNECs also displayed a significant reduction in secreted IL‐8 when compared to P. aeruginosa LPS alone (co‐treatment = 4.61 ± 0.29 ng/mL, P. aeruginosa LPS = 7.35 ± 0.89 ng/mL, p < 0.01). The drugs did not negatively impact TEER, paracellular permeability, LDH release, or CBF, indicating retention of cell integrity and function. Conclusion: Azithromycin decreased P. aeruginosa LPS IL‐8 production in HSNECs at drug concentrations attainable with sustained release of azithromycin from the CASS. In addition to antibacterial activity, anti‐inflammatory properties of the CASS should provide further benefit for patients with recalcitrant CRS.