Immunomodulatory Activity and Effectiveness of Macrolides in Chronic Airway Disease*Bruce K. Rubin and Markus O. Henke Chest 2004;125;70S-78S DOI 10.1378/chest.125.2_suppl.70SImmunomodulatory Activity and Effectiveness of Macrolides in Chronic Airway Disease* Interest in the immunomodulatory effects of mac- rolide antibiotics began with the observation that patients with severe asthma required lower doses of steroids if they also had received troleandomycin (TAO).1 Subsequently, macrolides have been studied for other airway diseases including diffuse panbron- chiolitis (DPB) and cystic fibrosis (CF). The most convincing demonstration of the immunomodulatory effects of macrolides has been in the treatment of DPB, a pulmonary disease of unknown etiology that is found primarily in Japan. In 1984, the 5-year survival rate for DPB was only 26%, but treatment with macrolides has dramatically increased the 10- year survival rate of these patients to 94%.2 The effectiveness of these drugs appears to be limited to the 14-membered and 15-membered macrolides, such as erythromycin, clarithromycin, and azithro- 70S mycin. These drugs improve pulmonary function, and decrease morbidity and mortality in patients with DPB.2–5 These macrolides decrease proinflam- matory cytokines in serum and BAL fluid (BALF), decrease mucus hypersecretion, and may protect the airway epithelium from damage.6 – 8 CF is similar to DPB in many ways including symptoms and pulmonary pathology. Both diseases are characterized by cough, persistent sinus disease, neutrophilic airway inflammation, susceptibility to persistent endobronchial infection with opportunis- tic pathogens, and progressive deterioration in pul- monary function, and both diseases are responsive to the immunomodulatory effects of macrolides. This article reviews the immunomodulatory effects of macrolides, and the evidence for their clinical effi- cacy for the treatment of DPB and CF. Macrolides as Biological Response Modifiers
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on September 11th, 2013
