Abstract
Introduction: IL-33, a member of the IL-1 cytokine family, mediates a range of pathologies including asthma and arthritis (Liew F.Y. et al. Nature Reviews Immunology, 2010; 10: 103-110). The mechanism by which IL-33 induces airway inflammation and the associated signalling pathways are incompletely understood. Rapamycin was initially described as a macrolide antibiotic that selectively blocks the mammalian target of rapamycin (mTOR), a serine/threonine kinase involved in numerous signaling pathways.
Aim: To identify the role of mTOR and rapamycin in IL-33-mediated airway inflammation.
Method: BALB/c mice were treated intranasally with 1 μg IL-33 daily with or without 1mg/kg rapamycin for 5 days. Airway inflammation was assessed on day 6 by bronchoalveolar lavage (BAL) cellularity and cytokine analysis.
Results: Intranasal IL-33 induced profound airway inflammation with increased cellular recruitment on BAL consisting mainly of macrophages and eosinophils. Treatment with rapamycin significantly reduced IL-33-mediated cellular recruitment (Figure 1A) and reduced both eosinophil (Figure 1B) and macrophage (Fig. 1C) influx into the airway.
Rapamycin also significantly reduced IL-33-mediated IL-5 and IL-13 production in BAL fluid.
Conclusions: Intranasal IL-33 induces airway inflammation that is partially blocked by treatment with intranasal rapamycin suggesting an important role for mTOR in the signaling pathway of IL-33 in vivo.
- © 2011 ERS
