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Published on: December 26, 2017
Anti-inflammatory activity of azithromycin attenuates the effects of lipopolysaccharide administration in mice
Vanesa Ivetić Tkalcević1, Berislav Bosnjak, Boska Hrvacić
1PLIVA Research Institute Ltd., Zagreb, Croatia. vanesa.ivetic-tkalcevic@pliva.hr
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.
Insights
Azithromycin, a macrolide antibiotic, demonstrates anti-inflammatory effects by reducing cytokines and cell migration. It improved survival in septic shock models, but its efficacy varied by administration route and model.
Area of Science:
- Pharmacology
- Immunology
- Microbiology
Background:
- Macrolide antibacterials possess anti-inflammatory properties.
- These properties may be beneficial in treating bacterial sepsis.
- Azithromycin's anti-inflammatory potential in sepsis warrants investigation.
Purpose of the Study:
- To investigate azithromycin's ability to mitigate lipopolysaccharide (LPS)-induced inflammation.
- To evaluate azithromycin's efficacy across three distinct LPS-induced inflammatory models.
Main Methods:
- Azithromycin administered intraperitoneally and orally in LPS-induced inflammatory models.
- Assessed plasma tumor necrosis factor-alpha (TNF-α) concentration.
- Evaluated survival rates in a septic shock model.
- Quantified inflammatory markers in bronchoalveolar lavage fluid (BALF).
Main Results:
- Azithromycin (10 and 100 mg/kg) significantly reduced plasma TNF-α levels in an intraperitoneal LPS model.
- Intravenous LPS challenge followed by azithromycin increased survival rates in a septic shock model.
- Intraperitoneal azithromycin improved inflammatory markers in BALF in an intranasal LPS model, while oral administration showed limited efficacy in reducing lung neutrophil infiltration.
Conclusions:
- Azithromycin exhibits significant anti-inflammatory properties.
- The effectiveness of azithromycin's anti-inflammatory actions is dependent on the experimental model and route of administration.
- Further research may optimize azithromycin dosing and delivery for sepsis treatment.
