Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In
addition to high levels of tissue penetration, whichmay counteract seemingly macrolide-resistant bacterial pathogens, these agents
also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the
innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses
during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly
effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the
treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways.
This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial
pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance.