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Published on: September 22, 2023
Azithromycin and ciprofloxacin inhibit interleukin-8 secretion without disrupting human sinonasal epithelial
Dong-Jin Lim1, Harrison M Thompson2, Christopher R Walz2
1Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.
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.
Insights
Azithromycin released from a novel sinus stent significantly reduced inflammation in human sinonasal cells. The stent maintained cell integrity and function, offering potential benefits for chronic rhinosinusitis patients.
Area of Science:
- Otolaryngology
- Infectious Diseases
- Pharmacology
Background:
- Chronic rhinosinusitis (CRS) often involves recalcitrant infections.
- A ciprofloxacin and azithromycin sinus stent (CASS) was developed to address these infections.
- Evaluating the anti-inflammatory effects of azithromycin released from CASS on sinonasal cells is crucial.
Purpose of the Study:
- To assess the anti-inflammatory activity of azithromycin released from the CASS.
- To determine the impact of azithromycin on primary human sinonasal epithelial cells (HSNECs) integrity and function.
Main Methods:
- HSNECs were stimulated with Pseudomonas aeruginosa lipopolysaccharide (LPS).
- Cells were treated with azithromycin and ciprofloxacin at concentrations relevant to CASS release.
- Interleukin-8 (IL-8) secretion, epithelial integrity (TEER, permeability, LDH), and ciliary beat frequency (CBF) were measured.
Main Results:
- Azithromycin significantly reduced IL-8 secretion in LPS-stimulated HSNECs across tested concentrations.
- Combined azithromycin and ciprofloxacin treatment also significantly reduced IL-8 compared to LPS alone.
- The tested drug concentrations did not compromise HSNEC integrity or function (TEER, permeability, LDH, CBF).
Conclusions:
- Azithromycin released from the CASS effectively reduces IL-8 production in HSNECs.
- The CASS demonstrates anti-inflammatory properties beyond its antibacterial activity.
- These findings suggest CASS could offer additional therapeutic benefits for patients with recalcitrant CRS.
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