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Feldman, Charles; Anderson, Ronald; Theron, Annette J.; Ramafi, Grace; Cole, Peter; Wilson, Robert

doi:10.1023/a:1027342424205

Cited by 46 publications

(6 citation statements)

References 40 publications

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“…Different macrolides, including AZM, were shown to stabilize human respiratory epithelium upon inflammatory in vitro conditions (Feldman et al, 1997). Beneficial effects of AZM on human airway epithelial integrity were then demonstrated by an increase of the transepithelial electrical resistance in human bronchial epithelial cells (Asgrimsson et al, 2006).…”

Section: Macrolides Enhance Airway Epithelial Integritymentioning

confidence: 99%

Could Azithromycin Be Part of Pseudomonas aeruginosa Acute Pneumonia Treatment?

et al. 2021

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Azithromycin (AZM) is a 15-membered-ring macrolide that presents a broad-spectrum antimicrobial activity against Gram-positive bacteria and atypical microorganisms but suffers from a poor diffusion across the outer-membrane of Gram-negative bacilli, including Pseudomonas aeruginosa (PA). However, AZM has demonstrated clinical benefits in patients suffering from chronic PA respiratory infections, especially cystic fibrosis patients. Since the rise of multidrug-resistant PA has led to a growing need for new therapeutic options, this macrolide has been proposed as an adjunctive therapy. Clinical trials assessing AZM in PA acute pneumonia are scarce. However, a careful examination of the available literature provides good rationales for its use in that context. In fact, 14- and 15-membered-ring macrolides have demonstrated immunomodulatory and immunosuppressive effects that could be of major interest in the management of acute illness. Furthermore, growing evidence supports a downregulation of PA virulence dependent on direct interaction with the ribosomes, and based on the modulation of several key regulators from the Quorum Sensing network. First highlighted in vitro, these interesting properties of AZM have subsequently been confirmed in the animal models. In this review, we systematically analyzed the literature regarding AZM immunomodulatory and anti-PA effects. In vitro and in vivo studies, as well as clinical trials were reviewed, looking for rationales for AZM use in PA acute pneumonia.

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Section: Macrolides Enhance Airway Epithelial Integritymentioning

confidence: 99%

Could Azithromycin Be Part of Pseudomonas aeruginosa Acute Pneumonia Treatment?

et al. 2021

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“…Macrolides may also decrease sputum production by inhibiting chloride secretion [68]. In addition to these anti-inflammatory effects of macrolides on epithelial cells, these agents have also been reported to protect ciliated respiratory epithelium against the damaging effects of host-derived bioactive phospholipids [89]. …”

Section: Effects Of Macrolides On Innate and Adaptive Immune Mechamentioning

confidence: 99%

Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

Steel

Theron

Cockeran

et al. 2012

Mediators of Inflammation

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Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance.

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“…During Pseudomonas aeruginosa infection in vitro, pretreatment with azithromycin prevented epithelial barrier dysfunction and enhanced recovery [57]. The potential protective effects of macrolides on human respiratory epithelium were investigated in vitro [58,59]. Macrolides, such as roxithromycin, clarithromycin, and azithromycin, reduced the production of reactive oxygen species generated by activated neutrophils [58].…”

Section: Epithelial Barrier Functionmentioning

confidence: 99%

The Mechanism of Action and Clinical Efficacy of Low-Dose Long-Term Macrolide Therapy in Chronic Rhinosinusitis

Ryu

Lee

Park

et al. 2023

IJMS

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Various chronic inflammatory airway diseases can be treated with low-dose, long-term (LDLT) macrolide therapy. LDLT macrolides can be one of the therapeutic options for chronic rhinosinusitis (CRS) due to their immunomodulatory and anti-inflammatory actions. Currently, various immunomodulatory mechanisms of the LDLT macrolide treatment have been reported, as well as their antimicrobial properties. Several mechanisms have already been identified in CRS, including reduced cytokines such as interleukin (IL)-8, IL-6, IL-1β, tumor necrosis factor-α, transforming growth factor-β, inhibition of neutrophil recruitment, decreased mucus secretion, and increased mucociliary transport. Although some evidence of effectiveness for CRS has been published, the efficacy of this therapy has been inconsistent across clinical studies. LDLT macrolides are generally believed to act on the non-type 2 inflammatory endotype of CRS. However, the effectiveness of LDLT macrolide treatment in CRS is still controversial. Here, we reviewed the immunological mechanisms related to CRS in LDLT macrolide therapy and the treatment effects according to the clinical situation of CRS.

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Untitled

Cited by 46 publications

References 40 publications

Could Azithromycin Be Part of Pseudomonas aeruginosa Acute Pneumonia Treatment?

Could Azithromycin Be Part of Pseudomonas aeruginosa Acute Pneumonia Treatment?

Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

The Mechanism of Action and Clinical Efficacy of Low-Dose Long-Term Macrolide Therapy in Chronic Rhinosinusitis

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