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Nonantimicrobial actions of macrolides : Overview and perspectives for future development

Nonantimicrobial actions of macrolides : Overview and perspectives for future development


Title: Nonantimicrobial actions of macrolides : Overview and perspectives for future development
Author: Kricker, Jennifer A.
Page, Clive P.
Gardarsson, Fridrik Runar
Baldursson, Olafur
Guðjónsson, Þórarinn
Parnham, Michael J.
Date: 2021
Language: English
Scope: 30
University/Institute: Landspitali - The National University Hospital of Iceland
Department: Faculty of Medicine
Clinical Laboratory Services, Diagnostics and Blood Bank
Series: Pharmacological Reviews; 73(4)
ISSN: 0031-6997
DOI: https://doi.org/10.1124/PHARMREV.121.000300
Subject: Gerlar; COVID-19; Sýklalyf; Macrolides; Pharmacology; Covid-19; Anti-bacterial agents; SARS-CoV-2; Molecular Medicine; Pharmacology
URI: https://hdl.handle.net/20.500.11815/3237

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Citation:

Kricker , J A , Page , C P , Gardarsson , F R , Baldursson , O , Guðjónsson , Þ & Parnham , M J 2021 , ' Nonantimicrobial actions of macrolides : Overview and perspectives for future development ' , Pharmacological Reviews , vol. 73 , no. 4 , pp. 233-262 . https://doi.org/10.1124/PHARMREV.121.000300

Abstract:

Macrolides are among the most widely prescribed broad spectrum antibacterials, particularly for respiratory infections. It is now recognized that these drugs, in particular azithromycin, also exert time-dependent immunomodulatory actions that contribute to their therapeutic benefit in both infectious and other chronic inflammatory diseases. Their increased chronic use in airway inflammation and, more recently, of azithromycin in COVID-19, how-ever, has led to a rise in bacterial resistance. An addi-tional crucial aspect of chronic airway inflammation, such as chronic obstructive pulmonary disease, as well as other inflammatory disorders, is the loss of epithelial barrier protection against pathogens and pol-lutants. In recent years, azithromycin has been shown with time to enhance the barrier properties of airway epithelial cells, an action that makes an important contribution to its therapeutic efficacy. In this article, we review the background and evidence for various immunomodulatory and time-dependent actions of macrolides on inflammatory processes and on the epithelium and highlight novel nonantibacterial mac-rolides that are being studied for immunomodulatory and barrier-strengthening properties to circumvent the risk of bacterial resistance that occurs with macro-lide antibacterials. We also briefly review the clinical effects of macrolides in respiratory and other inflammatory diseases associated with epithelial injury and propose that the beneficial epithelial effects of nonan-tibacterial azithromycin derivatives in chronic inflammation, even given prophylactically, are likely to gain increasing attention in the future. Significance Statement——Based on its immuno-modulatory properties and ability to enhance the protective role of the lung epithelium against pathogens, azithromycin has proven superior to other macrolides in treating chronic respiratory inflammation. A non-antibiotic azithromycin derivative is likely to offer prophylactic benefits against inflammation and epithelial damage of differing causes while preserving the use of macrolides as antibiotics.

Description:

Funding text Address correspondence to: Dr. Jennifer A. Kricker, EpiEndo Pharmaceuticals, Eidistorg 13-15, Innovation House, 170 Seltjarnarnes, Iceland. E-mail: jk@epiendo.com This work was supported by an Accelerator grant from the European Innovation Council [Grant 947081]. C.P.P. receives consultancy fees from EpiEndo Pharmaceuticals. J.A.K. and F.R.G. are full-time employees and M.J.P. and T.G. are part-time employees of EpiEndo Pharmaceuticals. Abstract submitted to 15th World Congress on Inflammation, 5–8 June, 2022, Rome, Italy. Jennifer A. Kricker, Bryndís Valdimarsdóttir, Jon Petur Joelsson, Sævar Ingthorsson, Mike J. Parnham, Snævar Sigurdsson, Ari Jón Arason, Ólafur Baldursson, Fridrik R. Gardarsson, Clive P. Page, Fredrik Lehmann, Thorarinn Gudjonsson. “Barriolides: Nonantibacterial compounds with epithelial barrier enhancing properties and anti-inflammatory effects in vitro.” Abstract submitted to 15th World Congress on Inflammation, 5–8 June, 2022, Rome, Italy. Jennifer A. Kricker, Sævar Ingthorsson, Michael J. Parnham, Bryndís Valdimarsdóttir, Jon Petur Joelsson, Snævar Sigurdsson, Fridrik R. Gardarsson, Clive P. Page, Ólafur Baldursson, Fredrik Lehmann, Thorarinn Gudjonsson. “Targeting the lung epithelial barrier to inhibit neutrophilic inflammation.” https://doi.org/10.1124/pharmrev.121.000300 Publisher Copyright: © 2021 by The Author(s).

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