title: Resolvin E1 promotes resolution of inflammation in a mouse model of an acute exacerbation of allergic asthma.
abstract: Endogenous mediators, such as RvE1 (resolvin E1), promote resolution of an inflammatory response and have potential as novel therapeutic agents. In the present study, we investigated the activity of RvE1 in a model of an acute exacerbation of chronic allergic asthma in mice. Animals sensitized to OVA (ovalbumin) received controlled low-level challenge with aerosolized antigen for 4 weeks, followed by a single moderate-level challenge to simulate an allergen-induced exacerbation of asthmatic inflammation. Induction of an exacerbation was associated with rapid recruitment of neutrophils, lymphocytes and eosinophils, together with increased levels of Th2 and pro-inflammatory cytokines. When administered before the final moderate-level challenge, RvE1 had only a modest effect on airway inflammation. To assess its effects when administered after induction of an exacerbation, we first characterized the cellular and molecular events associated with spontaneous resolution of airway inflammation over the following 96 h. Subsequently, we showed that administration of RvE1 at 2 and 8 h after the final challenge accelerated this process significantly. Specifically, RvE1 promoted a decline in the number of inflammatory cells, concentration of cytokines in lavage fluid and expression of mRNA for cytokines by macrophages, confirming its pro-resolution activity. In vitro, RvE1 had no apparent effect on lymphocytes, but suppressed significantly cytokine production by pulmonary macrophages, with evidence of down-regulation of the nuclear translocation of NF-κB (nuclear factor κB) p65 in these cells. The present study provides novel evidence that RvE1 can facilitate resolution of airway inflammation in a clinically relevant model of an acute exacerbation of asthma, possibly via its effects on activated pulmonary macrophages.
authors.affiliation: *Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Rylie P
authors.initials: RP
authors.lastname: Flesher
authors.affiliation: *Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Cristan
authors.initials: C
authors.lastname: Herbert
authors.affiliation: *Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Kumar
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006967:Hypersensitivity / Q000188:drug therapy* / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010047:Ovalbumin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D010047:Ovalbumin; D015118:Eicosapentaenoic Acid; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid