期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 539, 期 1-2, 页码 131-138出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2006.03.074
关键词
azithromycin; lipopolysaccharide; pulmonary neutrophilia; septic shock; TNF-alpha
Macrolide antibacterials inhibit the production of various cytokines and the migration of inflammatory cells. These anti-inflammatory actions of macrolides may be beneficial in attenuating inflammatory processes involved in bacteria] sepsis. Therefore, we investigated the ability of azithromycin to attenuate the deleterious effects of lipopolysaccharide (LPS), in three different LPS-induced inflammatory models. Our results show that azithromycin (10 and 100 mg/kg) significantly attenuated the intraperitoneal LPS-induced increase in plasma TNF-alpha concentration. It also increased survival rate in a septic shock model in mice challenged with intravenous LPS. Oral treatment with azithromycin (up to 300 mg/kg) was less effective in suppressing neutrophil infiltration into the lungs 24 h after intranasal LPS challenge, possibly because of a slower onset of action or inadequate dosing. In the same model, azithromycin given intraperitoneally significantly improved inflammatory markers (total cell number, neutrophil percentage and MIP-2 concentration) in bronchoalveolar lavage fluid. In conclusion, azithromycin exhibits significant anti-inflammatory properties but the potency of such effects varies depending on the experimental model and route of administration. (c) 2006 Elsevier B.V. All rights reserved.
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