Effect of Roxithromycin on Peripheral Neutrophil Adhesion Molecules in Patients with Chronic Lower Respiratory Tract Disease

Kusano, Shiro; Kadota, Jun‐ichi; Kohno, Shigeru; Iida, Kei; Kawakami, K.; Morikawa, Toru; Hara, Kohei

doi:10.1159/000196450

Cited by 38 publications

(21 citation statements)

References 15 publications

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“…Adhesion molecules are necessary for neutrophils and other inflammatory cells to migrate into the airway in response to inflammatory signals. Mac-1 (CD11b/CD18) expression on peripheral neutrophils from patients with DPB is higher than that on cells from healthy volunteers (159). Roxithromycin treatment caused a significant decrease in the expression of Mac-1, which was associated with decreased neutrophil numbers in BAL fluid.…”

Section: Effects On Inflammationmentioning

confidence: 86%

“…Roxithromycin treatment caused a significant decrease in the expression of Mac-1, which was associated with decreased neutrophil numbers in BAL fluid. There were no changes in lymphocyte function-associated antigen 1 (LFA-1) expression (159). Downregulation of the integrin CD11b/ CD18 has also been reported with erythromycin (173).…”

Section: Effects On Inflammationmentioning

confidence: 89%

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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: Effects On Inflammationmentioning

confidence: 86%

Section: Effects On Inflammationmentioning

confidence: 89%

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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“…Recent reports showed that roxithromycin is also effective for the treatment of chronic airway diseases such as diffuse panbronchiolitis, bronchial asthma, and chronic sinusitis [2][3][4]. Although the precise mechanism of actions of roxithromycin is unclear, it is reported that macrolide antibiotics have anti-inflammatory effects in various cells.…”

Section: Introductionmentioning

confidence: 99%

Roxithromycin Suppresses Mucin Gene Expression in Epithelial Cells

et al. 2004

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Macrolide antibiotics are believed to inhibit mucus secretion but the mechanism of action is unclear. This study was designed to investigate an effect of roxithromycin on MUC2 gene expression in cultured intestinal epithelial cells (HM3-MUC2 cells). A reporter gene assay was used for analysis. Roxithromycin suppressed MUC2 gene transcriptional activity in a dose-dependent manner in HM3-MUC2 cells. Phorbol 12-myristate 13-acetate (PMA), lipoteichoic acid (LTA), lipopolysaccharide (LPS) and leukotriene D₄ (LTD₄) significantly increased MUC2 luciferase activities in the following order: PMA > LTA > LTD₄ > LPS. Roxithromycin also decreased MUC2 gene transcriptional activity induced by PMA in a dose-dependent manner. NF-ĸB activation, but not AP-1 activation, was significantly suppressed by roxithromycin in HM3-MUC2 cells. A suppression of NF-ĸB activation was also observed in NCI-H292 cells. These results suggest that roxithromycin suppresses MUC2 gene expression in epithelial cells and that this suppression is probably via inhibition of NF-ĸB activation.

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Effect of Roxithromycin on Peripheral Neutrophil Adhesion Molecules in Patients with Chronic Lower Respiratory Tract Disease

Cited by 38 publications

References 15 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

Roxithromycin Suppresses Mucin Gene Expression in Epithelial Cells

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