Immunomodulatory properties of macrolides: Overview and historical perspective

Rubin, Bruce K.

doi:10.1016/j.amjmed.2004.07.021

Cited by 36 publications

(44 citation statements)

References 53 publications

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“…The effects of macrolides in patients with chronic inflammatory airway disease appear to be independent of antimicrobial properties. Immunomodulation, which differs from immunosuppression or anti-inflammation, is a nonlinear resetting of the inflammatory response by modifying or regulating one or more functions of the immune system (238). We use the term "immunomodulation" to describe the downregulation of a hyperimmunity or hyperinflammation without impairing the normal immune or inflammatory response to defend against infection.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

2010

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SUMMARY Macrolides have diverse biological activities and an ability to modulate inflammation and immunity in eukaryotes without affecting homeostatic immunity. These properties have led to their long-term use in treating neutrophil-dominated inflammation in diffuse panbronchiolitis, bronchiectasis, rhinosinusitis, and cystic fibrosis. These immunomodulatory activities appear to be polymodal, but evidence suggests that many of these effects are due to inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and nuclear factor kappa B (NF-κB) activation. Macrolides accumulate within cells, suggesting that they may associate with receptors or carriers responsible for the regulation of cell cycle and immunity. A concern is that long-term use of macrolides increases the emergence of antimicrobial resistance. Nonantimicrobial macrolides are now in development as potential immunomodulatory therapies.

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Section: Introductionmentioning

confidence: 99%

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

2010

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“…In recent years, there has been an increasing interest in the potential immunomodulatory properties of macrolides following the observation of the effectiveness of erythromycin in diffuse panbronchiolitis (DPB), an idiopathic disease found almost exclusively in the Far East and characterised by chronic recurrent bronchiolitis and peribronchiolitis with inflammatory infiltration of the small airways [4]. The immunomodulatory effects of macrolides, which are only seen with 14-(erythromycin, clarithromycin and roxithromycin) and 15-members (azithromycin) [5], may take several weeks to manifest, and include reduced airway mucus secretion and viscosity [6] and decreased airway neutrophil accumulation through a reduction in pro-inflammatory cytokines expression and adhesion molecule production [7][8][9] (fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Long-term macrolide treatment for chronic respiratory disease

2012

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Long-term macrolide treatment was first shown to alter the natural history of diffuse panbronchiolitis (DPB) in the late 1980s. Since then, macrolides have been demonstrated to exert antiinflammatory and immunomodulatory activity in addition to being antimicrobial. Indeed, their spectrum of action extends to the regulation of leukocyte function and production of inflammatory mediators, control of mucus hypersecretion, resolution of inflammation and modulation of host defence mechanisms. As such, the potential benefit of macrolide antibiotics has been evaluated in a variety of chronic respiratory diseases. The best studied condition is cystic fibrosis, of which there have been six randomised controlled trials showing evidence of benefit. However, most of the studies were limited by small numbers of patients and short follow-up. More recently, landmark studies have demonstrated the efficacy of azithromycin in reducing the risk of acute exacerbations in patients with chronic obstructive pulmonary disease, but the optimal duration and dosing of macrolide treatment remain uncertain.With the exception of patients with DPB and cystic fibrosis, until clear evidence of efficacy is available, the long-term use of macrolides should be limited to highly selected patients after careful evaluation of benefit and harm, or in the context of randomised controlled clinical trials. @ERSpublications Several studies evaluating macrolide antibiotics for the treatment of chronic respiratory diseases are underway

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“…The anti-inflammatory properties of macrolides are related to structure, with immunomodulatory effects seen with 14-(erythromycin, clarithromycin and roxithromycin) and 15-(azithromycin) but not 16-member (josamycin) macrolides [16]. In addition to the potential benefit, use of these agents also has the potential for harm.…”

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Long-term macrolide therapy in chronic inflammatory airway diseases

Crosbie¹,

Woodhead²

2008

Eur Respir J

120

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In addition to direct antibacterial actions, 14-and 15-member-ring macrolides have immune modulating effects that appear to be the reason for clinical benefit in diffuse panbronchiolitis.A literature search was conducted for studies of the clinical effectiveness of macrolides in other chronic lung conditions.A number of studies were identified that showed short-term beneficial outcomes or the potential for such outcomes in cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, asthma and post-transplant obliterative bronchiolitis. The studies were limited by small patient numbers, different outcome measures and short-term follow-up, and were not designed to assess potentially harmful effects.Further large prospective and long-term studies are required in order to identify potential benefit and harm before these agents can be recommended routinely for these conditions.

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Immunomodulatory properties of macrolides: Overview and historical perspective

Cited by 36 publications

References 53 publications

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

Long-term macrolide treatment for chronic respiratory disease

Long-term macrolide therapy in chronic inflammatory airway diseases

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