Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/97529
Title: Sepsis patients display a reduced capacity to activate nuclear factor-κB in multiple cell types
Authors: Hoogendijk, Arie J.
Garcia-Laorden, M. Isabel
Vught, Lonneke A. van
Wiewel, Maryse A.
Belkasim-Bohoudi, Hakima
Willem Duitman, Jan
Horn, Janneke
Schultz, Marcus J.
Scicluna, Brendon P.
Veer, Cornelis Van't
Vos, Alex F. de
Poll, Tom van der
Keywords: Immunosuppression
Septicemia -- Diagnosis
Flow cytometry -- Diagnostic use
Issue Date: 2017
Publisher: Lippincott Williams & Wilkins
Citation: Hoogendijk, A. J., Garcia-Laorden, M. I., van Vught, L. A., Wiewel, M. A., Belkasim-Bohoudi, H., Duitman, J., ... & van der Poll, T. (2017). Sepsis patients display a reduced capacity to activate nuclear factor-κB in multiple cell types. Critical Care Medicine, 45(5), e524-e531.
Abstract: Objectives: Sepsis is a complex clinical condition associated with high morbidity and mortality. A distinctive feature of sepsis is the reduced capacity of leukocytes to release proinflammatory cytokines in response to ex vivo stimulation. Cellular signaling events leading to immunosuppression in sepsis are not well defined. We investigated cell-specific signaling events underlying the immunosuppressed phenotype in sepsis.
Design: Ex vivo study.
Setting: ICU of an academic hospital.
Patients: Nineteen patients with sepsis and 19 age-matched healthy controls.
Interventions: None.
Measurements and main results: The phosphorylation state of p38 mitogen activated protein kinase and nuclear factor kappa-light-chain-enhancer of activated B cells were determined in ex vivo stimulated CD4 T cells, CD8 T cells, B cells, monocytes, and neutrophils. Messenger RNA expression levels of p38 mitogen activated protein kinase and nuclear factor kappa-light-chain-enhancer of activated B cells and negative regulators tumor necrosis factor-α-induced protein 3 (A20) and mitogen activated protein kinase phosphatase-1 were determined in neutrophils and peripheral blood mononuclear cells. Upon ex vivo stimulation, monocytes of sepsis patients were less capable in phosphorylating nuclear factor kappa-light-chain-enhancer of activated B cells. Sepsis was also associated with reduced phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells in stimulated B cells, CD4 and CD8 T cells. Messenger RNA expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells and A20 were diminished in peripheral blood mononuclear cells of sepsis patients, whereas p38 mitogen activated protein kinase messenger RNA was up-regulated. In neutrophils of sepsis patients, mitogen activated protein kinase phosphatase-1 messenger RNA levels were down-regulated.
Conclusions: Sepsis-induced immunosuppression associates with a defect in the capacity to phosphorylate nuclear factor kappa-light-chain-enhancer of activated B cells in lymphoid cells and monocytes.
URI: https://www.um.edu.mt/library/oar/handle/123456789/97529
Appears in Collections:Scholarly Works - FacHScABS

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