title: Anti-inflammatory activity of azithromycin attenuates the effects of lipopolysaccharide administration in mice.
abstract: 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.
authors.affiliation: PLIVA Research Institute Ltd., Zagreb, Croatia. vanesa.ivetic-tkalcevic@pliva.hr
authors.forename: Vanesa
authors.initials: V
authors.lastname: Ivetić Tkalcević
authors.forename: Berislav
authors.initials: B
authors.lastname: Bosnjak
authors.forename: Boska
authors.initials: B
authors.lastname: Hrvacić
authors.forename: Martina
authors.initials: M
authors.lastname: Bosnar
authors.forename: Nikola
authors.initials: N
authors.lastname: Marjanović
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Ferencić
authors.forename: Kristina
authors.initials: K
authors.lastname: Situm
authors.forename: Ognjen
authors.initials: O
authors.lastname: Culić
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parnham
authors.forename: Vesna
authors.initials: V
authors.lastname: Eraković
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D017963:Azithromycin / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D012772:Shock, Septic / Q000378:metabolism / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D017963:Azithromycin