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Paediatric Pulmonology and Allergology
2008 April, Vol. XI, No. 1 (3775-3793)
MACROLIDES BEYOND THE CONVENTIONAL ANTIMICROBIALS: A CLASS OF POTENT IMMUNOMODULATORS
Evangelos J. Giamarellos-Bourboulis
Attikon University Hospital, University of Athens, Greece
The historical change in the natural course of diffuse panbronchiolitis, a fatal disorder of the airways, following the introduction of erythromycin in its treatment has focused attention of researchers on the anti-inflammatory properties of macrolides. Chronic inflammation of the airways accompanied by infiltration by neutrophils and overproduction of mucus and proinflammatory cytokines is observed in bronchial asthma, cystic fibrosis, diffuse panbronchiolitis, chronic obstructive pulmonary disease and bronchiectasis. The airways of these patients are often colonized by mucoid Pseudomonas aeruginosa attached to epithelium by a biofilm. Bacteria intercommunicate for biofilm formation by a system of lactones known as quorum sensing. Macrolides inhibit mobility and quorum sensing of Pseudomonas aeruginosa; they also decrease nuclear factor-κB. Large randomized clinical trials for the management of these disorders with macrolides are not available, with sole exception of four trials denoting benefit following long-term administration of azithromycin in patients with cystic fibrosis. That benefit is consistent with increase in FEV1 and a decrease in the rate of bacterial exacerbations. Studies with small numbers of patients with chronic obstructive pulmonary disease revealed attenuation of the inflammatory reaction by macrolides. Experimental studies of Gram-negative sepsis have shown considerable attenuation of the systemic inflammatory response following intravenous administration of clarithromycin (International Journal of Antimicrobiol Agents, 2008; 31: 12–20, translation and publication with permission).