Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics.
Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may 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.
Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria and Tshwane Academic Division of the National Health Laboratory Service, P.O. Box 2034, Pretoria 0001, South Africa. hsteel@medic.up.ac.za
Helen C
HC
Steel
Annette J
AJ
Theron
Riana
R
Cockeran
Ronald
R
Anderson
Charles
C
Feldman
D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D018942:Macrolides / Q000494:pharmacology* / Q000627:therapeutic use*; D010586:Phagocytes / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D018942:Macrolides