Role of macrolides as immunomodular agents

In addition to being effective antimicrobial agents, macrolides have been associated with interesting nonantibacterial antiinflammatory properties. It appears that they may exert nontraditional antimicrobial effects against difficult organisms such as Pseudomonas aeruginosa by interfering with bacterial virulence factors (eg, alginate production, quorum-sensing mechanisms, biofilm formation). It has been suggested they have the potential for being used in the treatment of chronic airway inflammatory conditions. Growing evidence indicates that macrolides may exert disease-modifying effects in conditions such as asthma, cystic fibrosis, bronchiectasis, and in posttransplant bronchiolitis. They inhibit synthesis and/or secretion of proinflammatory cytokines, inhibit phagocytosis, decrease eosinophilic inflammation, increase mucociliary transport, reduce goblet cell secretion, decrease bronchoconstriction, and inhibit cholinergic responses of airway smooth muscle. Among the many factors involved in the inflammatory cascade, macrolides appear to interfere particularly with neutrophil recruitment and activation. Undoubtedly, the role of macrolides in the treatment of the inflammatory component of chronic disorders needs to be more firmly established.