title: The interleukin-6 G(-174)C polymorphism and the ex vivo interleukin-6 response to endotoxin in severely injured blunt trauma patients.
abstract: The aim of this study was to evaluate whether the -174 G/C promoter polymorphism of the interleukin-6 (IL-6) gene is associated with the ex vivo, whole blood IL-6 response to endotoxin with the development of severe sepsis in severely injured, blunt trauma patients. Patients with a severe trauma and an injury severity score of 16 were included in the study. The IL-6 -174 G/C promoter polymorphism was determined by real-time polymerase chain reaction (PCR) assay using specific fluorescence-labelled hybridisation probes. Whole blood of the patients was stimulated with endotoxin and the IL-6 concentrations were measured by ELISA. There was no association between the IL-6 -174 genotypes and the ex vivo, stimulated IL-6 response: 25% of the patients developed severe sepsis later in the clinical course. These patients had higher IL-6 concentrations following whole blood stimulation on day 1 (p = 0.046) after the trauma than patients with uncomplicated post-traumatic recovery. The difference was even more significant on day 2 after the trauma (p = 0.02). High IL-6 responses in a whole blood stimulation assay with endotoxin on days 1 and 2 after a trauma are associated with severe post-traumatic sepsis. Genotyping for the IL-6 -174 G/C polymorphism does not allow early identification of trauma patients with a high, ex vivo IL-6 synthesis capacity.
authors.affiliation: Department of Anesthesia, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1100 DD Amsterdam, The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Heesen
authors.forename: Udo
authors.initials: U
authors.lastname: Obertacke
authors.forename: F Ulrich
authors.initials: FU
authors.lastname: Schade
authors.forename: Brunhilde
authors.initials: B
authors.lastname: Bloemeke
authors.forename: Matthias
authors.initials: M
authors.lastname: Majetschak
mesh_terms: D001769:Blood / Q000187:drug effects* / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D018805:Sepsis / Q000209:etiology; D015599:Trauma Severity Indices; D014947:Wounds and Injuries / Q000097:blood* / Q000150:complications / Q000235:genetics
chemical_list: D004731:Endotoxins; D015850:Interleukin-6