title: Defective cytokine production early after multiple traumas: Modulation in severe sepsis.
abstract: The exact time frame of multiple trauma-induced immunosuppression and the immune mechanisms mediating transition to severe sepsis are largely unknown. Peripheral blood mononuclear cells were isolated from 69 patients with multiple injuries within the first 24h from injury and from 36 healthy volunteers and stimulated for cytokine production. Circulating endotoxins were measured by the kinetic LAL assay. Measurements were repeated the first 24h of sepsis onset. Patients had defective responses for tumour necrosis factor-alpha (TNFα), interleukin (IL)-10, IL-17 and interferon-gamma (IFNγ) using a broad-panel of bacterial stimuli. Production of IFNγ was pronounced for patients with trauma-related multiple organ failure (MOF). Thirty-six patients developed severe sepsis. At that time, production of TNFα was increased compared to baseline. The increase was greater among non-survivors than among survivors. Enhanced TNFα production on sepsis onset was a main finding of patients without endotoxemia. Immunosuppression of both innate and adaptive cytokine responses appears as early as the first 24h from injury. Transition into severe sepsis due to bacterial superinfection is accompanied by enhanced production of TNFα and this is linked with unfavorable outcome.
authors.affiliation: Intensive Care Unit, Korgialeneion Benakeion General Hospital, Athens, Greece.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Paraschos
authors.affiliation: Intensive Care Unit, Korgialeneion Benakeion General Hospital, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Patrani
authors.affiliation: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Pistiki
authors.affiliation: Intensive Care Unit, Korgialeneion Benakeion General Hospital, Athens, Greece.
authors.forename: Chrysostomos
authors.initials: C
authors.lastname: Katsenos
authors.affiliation: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tsaganos
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center & Radboud Center for Infectious Diseases, Nijmegen, The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece. Electronic address: egiamarel@med.uoa.gr.
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
authors.affiliation: Intensive Care Unit, Korgialeneion Benakeion General Hospital, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Mandragos
mesh_terms: D000328:Adult; D018988:Bacterial Translocation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D019446:Endotoxemia / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000276:immunology; D009104:Multiple Trauma / Q000276:immunology*; D018805:Sepsis / Q000276:immunology* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology
chemical_list: D016207:Cytokines; C508609:IL10 protein, human; C508717:IL17A protein, human; D020381:Interleukin-17; D015850:Interleukin-6; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Cytokines; Endotoxins; Outcome; Severe sepsis; Trauma