title: Macrolide antibiotics as immunomodulatory medications: proposed mechanisms of action.
abstract: Macrolide antibiotics administered in sub-antimicrobial doses improve pulmonary function and decrease exacerbation frequency for persons with diffuse panbronchiolitis or cystic fibrosis. Data also suggest a beneficial effect of macrolide antibiotics in the treatment of steroid dependent asthma. Many potential immunomodulatory effects of macrolide antibiotics have been reported including the ability to down-regulate prolonged inflammation, decreasing airway mucus secretion, inhibiting bacterial biofilm, decreasing the production of reactive oxygen species, inhibiting neutrophil activation and mobilization, accelerating neutrophil apoptosis, and blocking the activation of nuclear transcription factors. Macrolides initially decrease, then increase, and have finally a sustained suppression of cytokine secretions from normal human bronchial epithelial cells through inhibition and activation of extracellular signal-regulated kinases (ERK) and then reversibly retard cell proliferation probably through ERK. Consistent with this, macrolide antibiotics possibly reduce mucin production as well as neutrophil migration by interfering with ERK signal transduction.
authors.affiliation: Ministry of Defense and National Defense Medical College, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Shinkai
authors.forename: Markus O
authors.initials: MO
authors.lastname: Henke
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Rubin
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy / Q000276:immunology; D001249:Asthma / Q000188:drug therapy / Q000276:immunology; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy / Q000276:immunology; D001988:Bronchiolitis / Q000188:drug therapy / Q000276:immunology; D003240:Connective Tissue Diseases / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000276:immunology; D018942:Macrolides / Q000494:pharmacology* / Q000627:therapeutic use; D012220:Rhinitis / Q000188:drug therapy / Q000276:immunology; D012852:Sinusitis / Q000188:drug therapy / Q000276:immunology; D012871:Skin Diseases / Q000188:drug therapy / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D007155:Immunologic Factors; D018942:Macrolides