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Published on: September 12, 2019

A novel macrolide solithromycin exerts superior anti-inflammatory effect via NF-κB inhibition

Yoshiki Kobayashi1, Hiroo Wada, Christos Rossios

  • 1Airway Disease Section, National Heart and Lung Institute, Imperial College London, Guy Scadding Building, Royal Brompton Campus, Dovehouse Street, London SW3 6LY.

The Journal of Pharmacology and Experimental Therapeutics
|January 30, 2013
PubMed

Insights

A novel macrolide, solithromycin, demonstrates potent anti-inflammatory effects superior to existing macrolides for treating chronic obstructive pulmonary disease (COPD). It effectively reduces key inflammatory markers and may offer a promising new therapy.

Area of Science:

  • Pharmacology
  • Respiratory Medicine
  • Immunology

Background:

  • Macrolides can reduce exacerbations in chronic inflammatory respiratory diseases like COPD.
  • Current macrolides exhibit limited anti-inflammatory efficacy.
  • A novel macrolide/fluoroketolide, solithromycin (SOL), warrants investigation for enhanced anti-inflammatory properties.

Purpose of the Study:

  • To evaluate the anti-inflammatory effects of solithromycin (SOL) compared to existing macrolides.
  • To assess SOL's efficacy in reducing inflammatory mediators and cellular activity relevant to COPD.
  • To investigate SOL's impact on oxidative stress-induced inflammation and cigarette smoke-induced airway inflammation in vivo.

Main Methods:

  • Assessed SOL's effects on lipopolysaccharide-induced TNFα and CXCL8 release, MMP9 activity, and NF-κB activity in U937 cells and COPD patient PBMCs.
  • Compared SOL with erythromycin, clarithromycin, azithromycin, and telithromycin.
  • Examined SOL's effect on cigarette smoke-induced airway inflammation in a mouse model.

Main Results:

  • SOL exhibited superior inhibition of TNFα/CXCL8 production and MMP9 activity in U937 cells compared to other macrolides.
  • SOL suppressed TNFα release and MMP9 activity in COPD patient PBMCs at 10 µM, showing 10x greater potency than other macrolides.
  • SOL completely reversed oxidative stress-induced NF-κB activation and inhibited cigarette smoke-induced neutrophilia and pro-MMP9 production in vivo.

Conclusions:

  • Solithromycin displays significantly enhanced anti-inflammatory profiles compared to currently used macrolides.
  • SOL demonstrates potent inhibition of key inflammatory pathways implicated in COPD pathogenesis.
  • Solithromycin represents a promising candidate for future anti-inflammatory and antimicrobial therapy in COPD treatment.

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