Clinical implications of the immunomodulatory effects of macrolides.
Macrolide antibiotics are known for their efficacy in treating acute airway infections, but just as importantly, they are also effective anti-inflammatory agents. Their anti-inflammatory properties have been studied most thoroughly in chronic inflammatory airway diseases, particularly diffuse panbronchiolitis (DPB). Erythromycin, azithromycin, clarithromycin, and roxithromycin inhibit chemotaxis and infiltration of neutrophils into the airway and, subsequently, decrease mucus secretion. Mucus formation, a significant cause of morbidity and mortality in patients with chronic airway inflammation, is directly inhibited by macrolides and suppressed by decreased inflammation in the airway. The mechanisms of action for the anti-inflammatory properties of the macrolides are still being investigated, but they are clearly multifactorial. Macrolides inhibit the production of many proinflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor-alpha, perhaps by suppressing the transcription factor nuclear factor-kappaB or activator protein-1. Inhibition of cytokine production has been seen in vitro and also in bronchoalveolar lavage fluid, which contains less IL-8 and fewer neutrophils after treatment with macrolides. Macrolides also inhibit formation of leukotriene B4, which attracts neutrophils, and inhibit the release of superoxide anion by neutrophils that may be present in the airway. An important aspect of inflammation is extravasation of neutrophils into the tissues. Macrolides block formation of adhesion molecules necessary for neutrophil migration. Together, these anti-inflammatory effects result in improved pulmonary functions and fewer airway infections. In patients with DPB, the anti-inflammatory effects lead to a significant increase in survival. Further work is needed to characterize the clinical benefits of macrolides in patients with other chronic inflammatory airway diseases.
Tamaoki
Jun
J
First Department of Medicine, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shiinjuku, Tokyo, Japan.
Kadota
Junichi
J
Takizawa
Hajime
H
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002908:Chronic Disease; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007155:Immunologic Factors / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D008171:Lung Diseases / Q000150:complications / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D018942:Macrolides / Q000627:therapeutic use*; D009093:Mucus / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007155:Immunologic Factors; D018942:Macrolides