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Anti-inflammatory activity of azithromycin attenuates the effects of lipopolysaccharide administration in mice

2006; Elsevier BV; Volume: 539; Issue: 1-2 Linguagem: Inglês

10.1016/j.ejphar.2006.03.074

1879-0712

Vanesa Ivetić Tkalčević, Berislav Bošnjak, Boška Hrvačić, Martina Bosnar, Nikola Marjanović, Željko Ferenčić, Kristina Šitum, Ognjen Čulić, Michael J. Parnham, Vesna Eraković,

Pneumonia and Respiratory Infections

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-α 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.