Long Term Azithromycin in Cystic Fibrosis: Another Possible Mechanism of Action?

Abstract

Azithromycin is used for the treatment of cystic fibrosis lung disease, although its mechanisms of action are not completely understood. Besides its antiinflammatory and antimicrobial activities, one possibility could be the overexpression induction of the multidrug resistance-associated protein (MRP), which could affect chloride transport, thus overcoming the ion transport defect of cystic fibrosis. Seven patients were evaluated before and after 4 weeks of azithromycin treatment (500 mg once daily). Ion transport was studied in vivo by measuring nasal potential difference (NPD). MRP mRNA expression was studied in nasal cells by an internal standard-based semiquantitative RT-PCR assay. NPD was consistent with cystic fibrosis before treatment. After azithromycin treatment, sodium transport was still impaired, whereas a significant increase in chloride conductance was observed (p = 0.03). A significant direct correlation was found between MRP mRNA expression levels and NPD chloride response after azithromycin treatment (p = 0.04, r = 0.78). In conclusion, azithromycin may induce MRP overexpression and restore chloride conductance in the airways of cystic fibrosis patients. These findings suggest a new potential role of azithromycin in the treatment of cystic fibrosis pulmonary disease, i.e. the possibility to upregulate proteins whose function may, at least in part, compensate for the basic defect of cystic fibrosis.

Azithromycin Selectively Reduces Tumor Necrosis Factor Alpha Levels in Cystic Fibrosis Airway Epithelial Cells

“…However, the mechanisms of its efficacy are still unclear. Clinical beneficial effects of AZM might derive from the synergism of different effects, including inhibition of P. aeruginosa bacterial growth (29,44), decreased expression of bacterial virulence factors (39,44), modulation of the inflammatory response (41), ion transport (31), and tight junctions (3).…”

Застосування Азитроміцину В Клінічній Практиці

“…Механізм дії пре-парату при муковісцидозі комплексний і досі остаточно не з'ясований. Було встановлено, зокрема, що, окрім антимікробної й протизапальної дії, азитроміцин че-рез активацію специфічної мРНК покращує порушену провідність хлоридів у пацієнтів із муковісцидозом [32]. Важливою є також взаємодія препарату з Pseudomonas aeruginosa.…”

Macrólidos en enfermedades inflamatorias crónicas de las vías respiratorias

“…Aunque los estudios en las vías respiratorias se han centrado en MUC5AC principal de la mucina producida por las células caliciformes de superficie, el efecto de los macrólidos en la expresión de genes de mucina y / o la producción de proteínas se puede extender a otras mucinas y superficies epiteliales, por ejemplo, roxitromicina suprime la expresión génica MUC2 en cultivos de células epiteliales intestinales, el efecto consiste en la inhibición de la NFκB de señalización, como se indica en los estudios de análisis de periodista (42). En general, el efecto inhibitorio de los macrólidos en hipersecreción mucosa puede explicarse por su actividad inmunomoduladora, así como los efectos inhibidores directos de la actividad enzimática de la elastasa de los neutrófilos (43).…”