Ivetić Tkalcević Vanesa, Bosnjak Berislav, Hrvacić Boska, Bosnar Martina, Marjanović Nikola, Ferencić Zeljko, Situm Kristina, Culić Ognjen, Parnham Michael J, Eraković Vesna
PLIVA Research Institute Ltd., Zagreb, Croatia.
Eur J Pharmacol. 2006 Jun 6;539(1-2):131-8. doi: 10.1016/j.ejphar.2006.03.074. Epub 2006 Apr 6.
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 bacterial 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.
大环内酯类抗菌药物可抑制多种细胞因子的产生及炎性细胞的迁移。大环内酯类药物的这些抗炎作用可能有助于减轻细菌性脓毒症所涉及的炎症过程。因此，我们在三种不同的脂多糖（LPS）诱导的炎症模型中研究了阿奇霉素减轻脂多糖有害作用的能力。我们的结果表明，阿奇霉素（10毫克/千克和100毫克/千克）可显著减轻腹腔注射LPS诱导的血浆肿瘤坏死因子-α浓度升高。它还提高了静脉注射LPS攻击的小鼠脓毒症休克模型的存活率。在鼻内给予LPS 24小时后，口服阿奇霉素（高达300毫克/千克）在抑制中性粒细胞向肺部浸润方面效果较差，这可能是由于起效较慢或剂量不足。在同一模型中，腹腔注射阿奇霉素可显著改善支气管肺泡灌洗液中的炎症标志物（细胞总数、中性粒细胞百分比和巨噬细胞炎性蛋白-2浓度）。总之，阿奇霉素具有显著的抗炎特性，但这种作用的效力因实验模型和给药途径而异。
