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

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.

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