title: Lipid mediators in immune dysfunction after severe inflammation.
abstract: Sepsis, trauma, burns, and major surgical procedures activate common systemic inflammatory pathways. Nosocomial infection, organ failure, and mortality in this patient population are associated with a quantitatively different reprioritization of the circulating leukocyte transcriptome to the initial inflammatory insult, greater in both magnitude and duration, and secondary to multiple observed defects in innate and adaptive immune function. Dysregulation of inflammatory resolution processes and associated bioactive lipid mediators (LMs) mechanistically contribute to this phenotype. Recent data indicate the potential efficacy of therapeutic interventions that either reduce immunosuppressive prostaglandins (PGs) or increase specialized proresolving LMs. Here, we reassess the potential for pharmacological manipulation of these LMs as therapeutic approaches for the treatment of critical illness (CI).
authors.affiliation: Centre for Clinical Pharmacology, Division of Medicine, Rayne Institute, 5 University Street, University College London, London, WC1E 6JF, UK. Electronic address: james.fullerton@doctors.org.uk.
authors.forename: James N
authors.initials: JN
authors.lastname: Fullerton
authors.affiliation: Centre for Clinical Pharmacology, Division of Medicine, Rayne Institute, 5 University Street, University College London, London, WC1E 6JF, UK.
authors.forename: Alastair J
authors.initials: AJ
authors.lastname: O'Brien
authors.affiliation: Centre for Clinical Pharmacology, Division of Medicine, Rayne Institute, 5 University Street, University College London, London, WC1E 6JF, UK.
authors.forename: Derek W
authors.initials: DW
authors.lastname: Gilroy
mesh_terms: D000818:Animals; D016638:Critical Illness; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D018836:Inflammation Mediators / Q000378:metabolism*; D050356:Lipid Metabolism / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D018836:Inflammation Mediators
keywords: cyclooxygenase; eicosanoids; immunosuppression; prostaglandins; resolution of inflammation; sepsis