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Front. Immunol. | doi: 10.3389/fimmu.2018.00302

The immunomodulatory effects of macrolides – a systematic review of the underlying mechanisms

  • 1University of Melbourne, Australia
  • 2University Children’s Hospital Basel, Switzerland

Background: Macrolides have immunomodulatory properties. However, the mechanisms underlying the non-antimicrobial effects of macrolides are not well understood.
Objectives: To systematically review the current evidence of immunomodulatory properties of macrolides in humans and to describe the underlying mechanism and extend of their influence on the innate and adaptive immune system.
Methods: A systematic literature search was performed in MEDLINE using the OVID interface from 1946 to December 2016 according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA). Original articles reporting the influence of four macrolides (azithromycin, clarithromycin, erythromycin, roxithromycin) on immunological markers in humans were included.
Results: We identified 22 randomised, controlled trials, 16 prospective cohort studies and 8 case-control studies reporting on 47 different immunological markers (186 measurements) in 1777 patients. The most frequently reported outcomes were a decrease in the number of neutrophils, concentration of neutrophil elastase, interleukin (IL)-8, IL-6, IL-1beta, tumour necrosis factor-alpha, eosinophilic cationic protein, and matrix metalloproteinase 9. Inhibition of neutrophil function compared to eosinophils was more frequently reported. A decrease of T-helper (Th)2 cell cytokines (IL-4, IL-5, IL-6) was more frequently reported than a decrease of Th1 cytokines (IL-2, INF-gamma).
Conclusion: Macrolides influence a broad range of immunological mechanisms resulting in immunomodulatory effects. To further optimise the treatment of chronic inflammatory diseases by macrolides, further studies are necessary, particularly also comparing different macrolides and dose effect relationships.

Keywords: Azalides, Azithromycin, Clarithromycin, Erythromycin, immunolides, Roxithromycin

Received: 10 Nov 2017; Accepted: 02 Feb 2018.

Edited by:

Heiko Mühl, Goethe University Frankfurt, Germany

Reviewed by:

Michael R. Edwards, Imperial College London, United Kingdom
Klaus G. Schmetterer, Medizinische Universität Wien, Austria  

Copyright: © 2018 Zimmermann, Ziesenitz, Curtis and Ritz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Petra S. Zimmermann, University of Melbourne, Melbourne, Australia,