Immunomodulatory Effects of Macrolide Antibiotics

This is the authors' abstract. We don't add key points for this paper.

In Brief Macrolide antibiotics have been used for over 50 years to treat bacterial infections. Over the past 20 years, macrolide antibiotics have also been used to treat some chronic inflammatory airway diseases by virtue of their immunomodulatory properties. Macrolides have been reported to down-regulate prolonged inflammation or hyperinflammation by effects on cellular immunity, suppressing the production of pro-inflammatory cytokines and reactive oxygen species, blocking the activation of nuclear transcription factors, inhibiting neutrophil activation and mobilization, accelerating neutrophil apoptosis, and improving mucus clearance. Long-term, low-dose macrolide therapy has dramatically improved survival and decreased the frequency of exacerbation for persons with diffuse panbronchiolitis (DPB). In studies using azithromycin or clarithromycin, persons with cystic fibrosis (CF) had significantly improved lung function and fewer respiratory exacerbations compared with those taking a placebo. Macrolides are now first line therapy for DPB and recommended for the therapy for CF. Recent guidelines by the Japanese Ministry of Health and Welfare recommend for adults, erythromycin (EM) 400 or 600 mg/d, clarithromycin (CAM) 200 or 400 mg/d, roxithromycin (RXM) 150 or 300 mg/d, or azithromycin (AZM) 250 or 500 mg/d be given for at least 6 months and for up to 2 years. A clinical response is usually seen by the third month of therapy, and side effects are few and generally self-limited. Macrolides have been used as antibiotics for more than 5 decades, but in the past 20 years there has been increasing interest in their nonantimicrobial, immunomodulatory properties, especially for the therapy for chronic inflammatory airway diseases. Macrolides are now the mainstay of therapy for patients with diffuse panbronchiolitis and recommended for patients with cystic fibrosis. In this manuscript, we review the immunologic and clinical evidence supporting the appropriate use of macrolide antibiotics as immunomodulatory agents.