Low-Dose Azithromycin Attenuates OVA-Induced Airway Remodeling and Inflammation via Down-Regulating TGF-βl Expression in RAT

Abstract

Asthma is characteristic with chronic airway inflammation and remodeling. Azithromycin (AZM), the 15-member macrolide, is known to present an anti-inflammatory effect and is increasingly being used in the treatment of chronic inflammatory pulmonary diseases. We hypothesize that low-dose azithromycin can inhibit allergen-induced airway remodeling except allergic airway inflammation in rat model. Male SD rats underwent intraperitoneal ovalbumin sensitization on days 1 and 6 followed by an intranasal challenge on day 7–13. On day 14, airway inflammation and remodeling were assessed by quantifying leukocytes in the airway, expression of multiple inflammatory mediators in BALF, histological examination in lung and TGF-β1 mRNA and protein levels by qRT-PCR, immunohistochemistry and Western blotting. Treatment with low-dose azithromycin at the dose of 25 mg/kg significantly reduced ovalbumin-dependent airway inflammation, including accumulation of neutrophils, lymphocytes and eosinophils, secretion of IL-2, IL-4, IL-13 and TNF-α. Moreover, airway remodeling was significantly abrogated by azithromycin in this model. The mucus cell hyperplasia, thickening of the peribronchial smooth muscle layer, secretion of ET-1, IL-2, IL-4, IL-13 and TNF-α, and increasing mRNA and protein expressions of TGF-β1 in lung tissue were all significantly decreased in azithromycin-treated rats. These findings demonstrate the protective effect of low-dose azithromycin on allergic airway remodeling in rat and suggest low-dose azithromycin may have beneficial effects in treating allergic airway inflammation.