• Shock · Oct 2015

    T-10: CD56HI NK CELLS AS NOVEL PLAYERS IN IMMUNOSUPPRESSION AFTER POLYTRAUMA: IMPAIRED RESPONSIVENESS TO IL-12 CAUSES DEFICITS IN THE RESPONSE TO STAPHYLOCOCCUS AUREUS.

    • H Kleinertz, R Reinhardt, S Flohé, M Leenen, C Waydhas, and S B Flohé.
    • 1Department of Trauma Surgery, Surgical Research, University Hospital Essen, Germany 2Department of General-, Visceral- and Transplantation Surgery, University Hospital Essen, Essen, Germany 3Department of Trauma and Hand Surgery, University Hospital Duesseldorf, Duesseldorf, Germany 4Department of Orthopedics and Trauma Surgery, University Hospital Essen, Essen, Germany.
    • Shock. 2015 Oct 1;44 Suppl 2:23.

    IntroductionPolytrauma patients are at high risk for opportunistic infections due to the development of immunosuppression. During bacterial infections, the synthesis of Interleukin (IL) 12 triggers Natural Killer (NK) cells for the release of Interferon (IFN) gamma that stimulates phagocytes for the eradication of the pathogens.MethodsIn the present study, we investigated whether severe injury modulates the capacity of human NK cells to produce IFN-g in an in vitro model of Staphylococcus aureus infection. Blood mononuclear cells (PBMC) from 11 polytrauma patients (ISS > 16) were isolated at different time points (1 d to 3 weeks) after trauma and were stimulated with inactivated S. aureus bacteria. PBMC from healthy volunteers served as control.ResultsIndividual NK cells from patients were suppressed in IFN-g synthesis at any time point after trauma even in the presence of recombinant IL-12. The impaired IFN-g synthesis correlated with a reduced expression of the IL-12 receptor (IL-12R) beta2 chain and downstream with decreased Signal Transducer and Activator of Transcription (STAT) 4 phosphorylation. When PBMC were exposed to S. aureus in the absence of autologous serum, NK cells increased the production of IFN-g and the expression of the IL-12R beta2 except NK cells from patients on d 8 after trauma. Transfer of patients' sera on PBMC of healthy volunteers led to a reduced S. aureus-induced IFN-g production, IL-12R beta2 expression, and STAT4 phosphorylation in/on NK cells.ConclusionThe suppressed NK cell function after severe injury is associated with disturbed IL-12 signal transduction and might contribute to the increased susceptibility to infections after polytrauma.

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