title: The anti-inflammatory and proresolving mediator resolvin E1 protects mice from bacterial pneumonia and acute lung injury.
abstract: Whereas pneumonia is the most common cause of death and disability worldwide, most cases of pneumonia spontaneously resolve. Mechanisms that promote pneumonia resolution remain to be determined. Resolvin E1 (RvE1) is an endogenous mediator that displays proresolving actions in sterile inflammation. In this study, we developed a new model of aspiration pneumonia to evaluate the effect of RvE1 on acute lung injury caused by acid aspiration and subsequent bacterial challenge. Mice received hydrochloric acid into the left lung followed by the enteric pathogen Escherichia coli. I.v. administration of RvE1 (approximately 0.005 mg/kg) prior to acid injury selectively decreased lung neutrophil accumulation by 55% and enhanced clearance of E. coli. RvE1 significantly decreased lung tissue levels of several proinflammatory chemokines and cytokines, including IL-1beta, IL-6, HMGB-1, MIP-1alpha, MIP-1beta, keratinocyte-derived chemokine, and MCP-1, in a manner independent of the anti-inflammatory mediators IL-10 and lipoxin A4. In addition, animals treated with RvE1 had a marked improvement in survival. These findings in experimental aspiration pneumonia have uncovered protective roles for RvE1 in pathogen-mediated inflammation that are both anti-inflammatory for neutrophils and protective for host defense, suggesting that RvE1 represents the first candidate for a novel therapeutic strategy for acute lung injury and pneumonia that harnesses natural resolution mechanisms.
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Seki
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Ryo
authors.initials: R
authors.lastname: Taguchi
authors.forename: Taku
authors.initials: T
authors.lastname: Miyasho
authors.forename: Rina
authors.initials: R
authors.lastname: Takamiya
authors.forename: Koichiro
authors.initials: K
authors.lastname: Asano
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
authors.forename: Junzo
authors.initials: J
authors.lastname: Takeda
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Levy
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001424:Bacterial Infections / Q000188:drug therapy*; D016207:Cytokines / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004926:Escherichia coli; D018836:Inflammation Mediators; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D011014:Pneumonia / Q000188:drug therapy*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D015118:Eicosapentaenoic Acid; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid