Macrolides protect against Pseudomonas aeruginosa infection via inhibition of inflammasomes.

Macrolides antibiotics have been effectively used in many chronic diseases, especially with Pseudomonas aeruginosa (P. aeruginosa) infection. The mechanisms underlying the therapeutic effects of macrolides in these diseases remain poorly understood. We established a mouse model of chronic lung infection using P. aeruginosa agar-beads, with azithromycin treatment or placebo. Lung injury, bacterial clearance, and inflammasome-related proteins were measured. In vitro, the inflammasomes activation induced by flagellin or ATP were assessed in LPS-primed macrophages with or without macrolides treatment. Plasma IL-18 levels were determined from patients who were diagnosed with bronchiectasis isolated with or without P. aeruginosa and treated with azithromycin for 3-5 days. Azithromycin treatment enhanced bacterial clearance and attenuated lung injury in mice chronically infected with P. aeruginosa, which resulted from the inhibition of caspase-1-dependent IL-1ß and IL-18 secretion. In vitro, azithromycin and erythromycin inhibited NLRC4 and NLRP3 inflammasomes activation. Plasma IL-18 levels were higher in bronchiectasis patients with P. aeruginosa isolation compared with healthy controls. Azithromycin administration markedly decreased IL-18 secretion in bronchiectasis patients. The results of this study reveal that azithromycin and erythromycin exert a novel anti-inflammatory effect by attenuating inflammasomes activation, which suggests potential treatment options for inflammasome-related diseases.

Bronchiectasis in China.

Bronchiectasis is a common but long-neglected disease in China, causing a substantial disease burden both to patients and to society. The overall prevalence of physician-diagnosed bronchiectasis in people aged 40 years or older is estimated at 1.2% and is trending upward with aging of the population. The etiology of bronchiectasis has not been identified heretofore in more than 70% of patients in China, although pneumonia and tuberculosis still appear to be the most common causes of acquired bronchiectasis. Etiologies, comorbidities, and infecting organisms vary greatly across previously published epidemiological studies, resulting in considerable uncertainty. Little is known about the spectrum of severity of bronchiectasis in China. Presently, engagement of pulmonologists is largely limited to acute treatment of exacerbations of severe bronchiectasis. Based on limited available data and expert consensus, the first comprehensive guidelines for the diagnosis and treatment of bronchiectasis in China were published in 2012. Research to advance medical care for patients with this disease in China should focus on several priorities, including: standardization of diagnostic criteria with appropriate application of computed tomographic imaging; use of validated multidimensional grading systems to assess the severity of bronchiectasis; and epidemiological studies that are designed to measure mild to moderate as well as severe disease, and to represent the population beyond large urban centers. Better estimates of the true burden of bronchiectasis are needed to guide allocation of national medical resources and to implement public health strategies for prevention of the disease. Treatment should be expanded to include expert maintenance care of ambulatory patients in addition to treatment of exacerbations.