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Inhibition of neutrophil inflammatory mediator expression by azithromycin

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Abstract

Background and objective

Peri-implant tissues appear to exhibit a more vigorous inflammatory response during post-operative healing than periodontal tissues. There is evidence that a single dose of amoxicillin (AMX) prior to implant surgery reduces the risk of early peri-implant healing complications. This study compared the effects of AZM and AMX on neutrophil expression of mRNA for mediators involved in peri-implant healing.

Materials and methods

Neutrophils were isolated from healthy human donors and pre-incubated with AZM (4 or 8 μg/ml) or AMX (2 or 4 μg/ml). Cells were then incubated with LPS (1 μg/ml), TNF-α (10 ng/ml), or medium alone (control) for 1, 2, and 4 h. Total RNA was analyzed with qPCR to quantify changes in expression of the six inflammatory mediators.

Results

LPS and TNF-α induced a similar pattern of IL-1β mRNA expression, with peak expression at 1 h. For most mediators, gene expression in neutrophils activated by LPS was markedly reduced in a dose-dependent manner by AZM. Therapeutic concentrations of AZM (8 μg/ml) consistently reduced expression of mediators tested in this study. AMX was effective only in a few cases and under certain conditions. Therefore, AZM was more effective in its direct anti-inflammatory action.

Conclusion

AZM is a consistent and effective inhibitor of neutrophil inflammatory mediator mRNA expression.

Clinical relevance

Given that a single dose of AZM produces higher and more sustained concentrations of this agent in periodontal tissues than AMX when used as a pre-operative prophylactic antibiotic, AZM has greater potential to inhibit inflammatory mediator expression at peri-implant wound sites than AMX.

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Acknowledgments

The authors thank Dr. Robert Schifferle (Department of Periodontics and Endodontics, School of Dental Medicine, the State University of New York at Buffalo) for providing purified LPS from Porphyromonas gingivalis.

Funding

This work was supported by an internal grant from the Ohio State University College of Dentistry in Columbus, OH, USA.

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Authors and Affiliations

  1. School of Dentistry, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, T6G 1C9, Canada

    Monica P. Gibson

  2. Division of Periodontology, College of Dentistry, The Ohio State University, 3015 Postle Hall, 305 W. 12th Ave, Columbus, OH, 43210, USA

    Monica P. Gibson & John D. Walters

Authors
  1. Monica P. Gibson
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Correspondence to John D. Walters.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (reviewed by the Ohio State University Biomedical Sciences Institutional Review Board as study number 2014H0245) and with the 1964 Helsinki declaration and it later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Gibson, M.P., Walters, J.D. Inhibition of neutrophil inflammatory mediator expression by azithromycin. Clin Oral Invest 24, 4493–4500 (2020). https://doi.org/10.1007/s00784-020-03314-4

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