Macrolide activities beyond their antimicrobial effects: macrolides in diffuse panbronchiolitis and cystic fibrosis

Diffuse panbronchiolitis (DPB) is a pulmonary disease characterized by chronic inflammation of the bronchioles and chronic infiltration of inflammatory cells in the lungs. DPB has several features in common with cystic fibrosis (CF). Clinical trials in patients with DPB or CF suggest a potential role for maintenance (long-term and low-dose) macrolide therapy in the treatment of these chronic pulmonary conditions. Indeed, these studies demonstrate improved clinical and physiological states with macrolide therapy. The beneficial effects of long-term low-dose macrolides are not related to their antimicrobial properties, since levels of macrolides with low-dose treatment are too low to have sufficient antimicrobial effects. Data indicate that macrolides may have immunomodulatory activities: (1) in vitro and ex vivo studies clearly show that macrolides can influence cytokine production by several cell types; (2) furthermore, macrolides can alter polymorphonuclear cell functions in vitro and ex vivo. Although immunomodulation may serve as one explanation for the beneficial effects of macrolides in patients with chronic pulmonary inflammation, the effect of low-dose macrolide therapy on biofilm-formation may form a second explanation for the positive effects of long-term low-dose macrolide therapy. In the present paper, the clinical trials on maintenance macrolide therapy in patients with DPB or CF are reviewed. This is followed by a discussion on the immunomodulating effects of macrolides, and the effects of macrolides on biofilm formation.