The Immunomodulatory Effects of Macrolides—A Systematic Review of the Underlying Mechanisms

Abstract

BackgroundThe mechanisms underlying the non-antimicrobial immunomodulatory properties of macrolides are not well understood.ObjectivesTo systematically review the evidence for the immunomodulatory properties of macrolides in humans and to describe the underlying mechanism and extent of their influence on the innate and adaptive immune system.MethodsA systematic literature search was done 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 investigating the influence of four macrolides (azithromycin, clarithromycin, erythromycin, and roxithromycin) on immunological markers in humans were included.ResultsWe identified 22 randomized, controlled trials, 16 prospective cohort studies, and 8 case–control studies investigating 47 different immunological markers (186 measurements) in 1,834 participants. The most frequently reported outcomes were a decrease in the number of neutrophils, and the concentrations of neutrophil elastase, interleukin (IL)-8, IL-6, IL-1beta, tumor necrosis factor (TNF)-alpha, eosinophilic cationic protein, and matrix metalloproteinase 9. Inhibition of neutrophil function was reported more frequently than eosinophil function. A decrease in T helper (Th) 2 cells cytokines (IL-4, IL-5, IL-6) was reported more frequently than a decrease in Th1 cytokines (IL-2, INF-gamma).ConclusionMacrolides influence a broad range of immunological mechanisms resulting in immunomodulatory effects. To optimize the treatment of chronic inflammatory diseases by macrolides, further studies are necessary, particularly comparing different macrolides and dose effect relationships.

Mycoplasma pneumoniae detection in children with respiratory tract infections and influence on management – a retrospective cohort study in Switzerland

“…However, data on the efficacy of macrolide treatment are controversial. Two recent systematic reviews concluded that there is insufficient evidence to draw conclusions about the efficacy of macrolides in the treatment of M. pneumoniae lower RTIs in children, despite the fact that there is considerable evidence on anti-inflammatory properties of these agents (26)(27)(28). Interestingly, in our study, no short-term treatment benefit such as reduced oxygen requirement or shorter hospital stay was found when comparing patients with empiric administration of a macrolide and those with prescription 48 hours later after M. pneumoniae infection had been confirmed by nucleic acid amplification testing.…”

COVID-19 for the Cardiologist

“…Azithromycin, a macrolide antibiotic, has long been touted for its anti-inflammatory effect and has been used as adjunctive therapy in treatment of community acquired pneumonia and chronic obstructive pulmonary disease exacerbations (147). Limited data suggest that adjunctive azithromycin in moderate-severe ARDS is associated with improved outcomes (148).…”

Bronchoalveolar lavage cytokines are of minor value to diagnose complications following lung transplantation

“…The diagnosis of CLAD is an indication to treat patients with an immunomodulatory macrolide. As such, even if the absolute number of patients receiving macrolides at our institution during the first year after lung transplantation is low, a bias of such treatment for cytokine distribution in BAL cannot be excluded [54]. Fifth, statistical methods were not used to adjust for storage time of the BAL samples, number of analyses per patient and date of collection after transplantation.…”