Clinical implications of the immunomodulatory effects of macrolides
Clinical implications of the immunomodulatory effects of macrolides
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DOI：
10.1016/j.amjmed.2004.07.023
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发表时间：
2004-11-08
影响因子：
5.9
通讯作者：
Takizawa, H
中科院分区：
文献类型：
--
作者：
Tamaoki, J;Kadota, J;Takizawa, H
大环内酯类抗生素因其治疗急性呼吸道感染的疗效而闻名，但同样重要的是，它们也是有效的抗炎药。它们的抗炎作用在慢性炎症性呼吸道疾病，特别是弥漫性泛细支气管炎(DPB)中得到了最彻底的研究。红霉素、阿奇霉素、克拉霉素和罗红霉素可抑制中性粒细胞的趋化和中性粒细胞向呼吸道的渗透，从而减少粘液分泌。粘液形成是慢性呼吸道炎症患者发病率和死亡率的重要原因，它直接被大环内酯类化合物抑制，并通过减少呼吸道炎症而被抑制。大环内酯类化合物的抗炎作用机制仍在研究中，但它们显然是多因素的。大环内酯类化合物可能通过抑制转录因子核因子-kappaB或激活蛋白-1来抑制许多促炎细胞因子的产生，如IL-1、IL-6、IL-8和肿瘤坏死因子-a。细胞因子的产生在体外和支气管肺泡灌洗液中都受到了抑制，在用大环内酯类药物治疗后，肺泡灌洗液中含有较少的IL-8和较少的中性粒细胞。大环内酯类还抑制白三烯B-4的形成，白三烯B-4吸引中性粒细胞，并抑制可能存在于呼吸道中的中性粒细胞释放超氧阴离子。炎症的一个重要方面是中性粒细胞渗入组织。大环内酯类化合物可阻断中性粒细胞迁移所必需的黏附分子的形成。总而言之，这些抗炎作用可以改善肺功能，减少呼吸道感染。在DPB患者中，抗炎作用显著提高了存活率。需要进一步的工作来确定大环内酯类药物在其他慢性炎症性呼吸道疾病患者中的临床益处。
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-a, 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 B-4, 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.