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Azithromycin and ciprofloxacin inhibit interleukin‐8 secretion without disrupting human sinonasal epithelial integrity in vitro
Author(s) -
Lim DongJin,
Thompson Harrison M.,
Walz Christopher R.,
Ayinala Samrath,
Skinner Daniel,
Zhang Shaoyan,
Grayson Jessica W.,
Cho DoYeon,
Woodworth Bradford A.
Publication year - 2021
Publication title -
international forum of allergy and rhinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.503
H-Index - 46
eISSN - 2042-6984
pISSN - 2042-6976
DOI - 10.1002/alr.22656
Subject(s) - azithromycin , ciprofloxacin , medicine , pseudomonas aeruginosa , microbiology and biotechnology , pharmacology , paracellular transport , lipopolysaccharide , immunology , antibiotics , biology , permeability (electromagnetism) , bacteria , biochemistry , genetics , membrane
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.