Anti‐inflammatory effects of macrolides in lung disease*

Abstract

During the past five decades there has been increasing interest in the potential anti-inflammatory effects of macrolide antibiotics. Low-dose macrolide therapy has dramatically increased survival in patients with diffuse panbronchiolitis, a disease with many similarities to cystic fibrosis (CF). This has led to further investigation into the potential use of macrolides in chronic lung diseases with an inflammatory component. This review summarizes the proposed anti-inflammatory mechanisms for this group of antibiotics, and examines the effect of macrolides on modulation of the inflammatory pathways, neutrophil function, bronchoconstriction, Pseudomonas biofilm, mucus rheology, bacterial adherence, and multidrug-resistant protein. It discusses the current status of clinical studies in children with CF, bronchiectasis, and asthma. While there are much in vitro data for different proposed anti-inflammatory effects, randomized controlled clinical trials in children with CF, bronchiectasis, and asthma are still just beginning. The benefits and potential side effects need to be determined before routine use can be advised.

A dichotomy in bronchiolitis obliterans syndrome after lung transplantation revealed by azithromycin therapy

“…The beneficial effect of macrolides in different lung disorders and in LTx is believed to be at least partially attributable to the anti-inflammatory properties of the drugs [7]. Recently, a 3-month follow-up study on azithromycin therapy for patients diagnosed with BOS was published [8].…”

Diffuse Panbronchiolitis is not Restricted to East Asia—a Mini Literature Review

“…Since macrolide levels in the airways of patients with DBP are well below the minimal level to exhibit antibacterial effects, anti-inflammatory and immuno-modulatory effects can be attributed to a beneficial effect of low-dose, long-term macrolide therapy. 53 Established diagnostic criteria and treatment guidelines are well known in East Asian countries where the disease incidence is higher. But, as is evident from case studies in this article, the emerging global footprint of this disease raises concerns.…”

Efeito anti-inflamatório dos macrolídeos em doenças pulmonares da infância

“…(1) Macrolides are known not only for their bacteriostatic effect but also for having an anti-inflammatory effect (reducing neutrophil counts). (5) Although the pathogenesis of asthma is complex, the importance of inflammatory cells and pro-inflammatory cytokine secretion is recognized, the major cells being Th2, eosinophils, and mast cells. (40) The positive effect of macrolides is controversial in various studies of asthma patients.…”

“…(1,3,4) The antiinflammatory mechanism of macrolides was originally discovered in Japan in the 1980s, when treatment with macrolides significantly increased survival in patients with diffuse panbronchiolitis (DPB), a severe chronic lung disease with intense neutrophilic inflammation. (5) Among the most important effects of macrolides are the inhibition of pro-inflammatory cytokine synthesis and secretion and the increase in antiinflammatory cytokine secretion, as well as effects on neutrophil activity via inhibition of neutrophil migration to sites of inflammation. (6,7) Macrolides can also inhibit leukocyte degranulation, reduce eosinophilic inflammation, activate macrophage phagocytic activity, (7) and increase mucociliary transport, reducing mucus production in vivo (8,9) and in vitro.…”