Oral Presentation 6th Australian Health and Medical Research Congress 2012

Resolvin E1 promotes resolution of inflammation in a model of an acute exacerbation of allergic asthma (#216)

Rylie P. Keogh 1 , Cristan Herbert 1 , Rakesh K. Kumar 1
  1. School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia

Background: Resolution of an inflammatory response is in part an active process. Recently, several lipid-derived endogenous mediators have been described which are agonists for pathways that limit inflammation and/or promote clearance of inflammatory cells. Resolvin E1 (RvE1) is one such pro-resolution mediator, currently undergoing early clinical testing. In a model of an acute exacerbation of allergic asthma, we defined the cellular and molecular events associated with spontaneous resolution of airway inflammation, and assessed the capacity of RvE1 to accelerate this process.  Methods: Female BALB/c mice, systemically sensitised to ovalbumin, were repeatedly challenged with a low mass concentration (≈3 mg/m3) of aerosolised ovalbumin for 4 weeks to induce changes of mild chronic asthma, then received a single moderate-level challenge (≈30 mg/m3) to trigger inflammatory changes of an acute exacerbation. To characterise spontaneous resolution, cell numbers and expression of cytokines in bronchoalveolar lavage fluid and lung tissue were quantified between 4-96 hours. To assess the pro-resolution activity of RvE1, mice were administered 1 μg of RvE1 intraperitoneally 2 and 8 hours after the final moderate-level challenge, and examined at 4, 12 and 24 hours. Results: Induction of an experimental acute exacerbation of asthmatic inflammation was associated with recruitment of neutrophils, lymphocytes and eosinophils, peaking at 12 hours, and subsequent recruitment of macrophages. Most pro-inflammatory and Th2 cytokines in lavage fluid reached maximal levels at 4 hours and returned to normal by 36 hours. Similar patterns of response were observed for expression of cytokines in airway tissue and by pulmonary macrophages. Treatment with RvE1 significantly decreased numbers of inflammatory cells, concentrations of various cytokines in lavage fluid, and expression of mRNA for pro-inflammatory cytokines by macrophages. Conclusions: This study provides novel evidence that RvE1 can facilitate resolution of established airway inflammation in a clinically relevant model of an acute exacerbation of asthma.