Patients with sepsis exhibit mitochondrial biogenesis in peripheral blood immune cells.

Sjovall F, Morota S, Persson J, Hansson MJ, Elmer E.
Journal   Critical Care
Species  
Analytes Measured   IL-6
Matrix Tested   Plasma
Year   2013
Volume   17
Page Numbers   152
Application   Cytokines and Chemokines
Abstract
Background: Sepsis is one of the leading causes of admission to the ICU. After the initial proinflammatory response a gradual change towards a more anti-inflammatory pattern can be seen. In this latter stage, immune cell function has been suggested to be downregulated leading to an immunoparalysis, lending the patient more vulnerable to deleterious secondary infections. Mitochondrial dysfunction has been suggested to play a role in this immunoparalytic state and we therefore investigated mitochondrial respiratory function in peripheral blood immune cells (PBICs) in patients with sepsis and its evolvement over time.

Methods: Twenty patients with severe sepsis or septic shock were included. PBICs were isolated from freshly drawn blood via density gradient centrifugation and analyzed three times during the first week after admission to the ICU (within 48 hours, days 3 to 4 and days 6 to 7). Mitochondrial respiration was examined with high-resolution respirometry in intact and permeabilized cells in order to evaluate both whole cell respiration as well as contribution of individual complexes. Mitochondrial DNA (mtDNA), cytochrome c (Cyt c) and citrate synthase (CS) were measured as indicators of change in cellular mitochondrial content.

Results: In intact PBICs from septic patients, with endogenous substrates, there was a gradual increase in cellular respiration that was 73% higher after 1 week compared with controls (P = 0.003). In permeabilized cells, complex I, II and IV displayed increased respiration compared with controls already at days 1 to 2 (37%, 30% and 73% respectively, P < 0.001) and continued to increase to days 6 to 7 (68%, 68% and 108% respectively). The rise in mitochondrial respiration was paralleled by higher levels of CS activity and increased mtDNA and Cyt c content in cells from septic patients (90%, 143% and 231% for the respective parameter at days 6 to 7 compared with controls, P < 0.0001). Mortality for the septic patients was 25% by day 7. There was no difference in respiratory capacity between survivors and nonsurvivors at any of the time points measured.

Conclusion: In PBICs from patients with severe sepsis or septic shock there is a gradual increase in mitochondrial respiratory capacity. This increase is probably due to mitochondrial biogenesis as indicated by increases in mitochondria-specific markers. Nonsurvivors displayed the same increase in respiration as survivors arguing against mitochondrial respiratory dysfunction and defect mitochondrial biogenesis, in PBICs, as a mediator of increased mortality in the septic condition.

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IL-6
V-PLEX Human Cytokine 30-Plex Kit
Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Human IL-6 Kit
IL-6 | Human
Singleplex
V-PLEX Human Proinflammatory Panel I (4-Plex)
IFN-γ, IL-1β, IL-6, TNF-α | Human
Multiplex
V-PLEX Human Proinflammatory Panel II (4-Plex)
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
V-PLEX Mouse IL-6 Kit
IL-6 | Mouse
Singleplex
V-PLEX Plus Human Cytokine 30-Plex Kit
Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Plus Human IL-6 Kit
IL-6 | Human
Singleplex
V-PLEX Plus Human Proinflam. Panel I (4-Plex)
IFN-γ, IL-1β, IL-6, TNF-α | Human
Multiplex
V-PLEX Plus Human Proinflam. Panel II (4-Plex)
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
V-PLEX Plus Mouse IL-6 Kit
IL-6 | Mouse
Singleplex
V-PLEX Plus Proinflammatory Panel 1 Human Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Multiplex
V-PLEX Plus Proinflammatory Panel1 Mouse Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, KC/GRO, TNF-α | Mouse
Multiplex
V-PLEX Plus Rat IL-6 Kit
IL-6 | Rat
Singleplex
V-PLEX Proinflammatory Panel 1 Human Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Multiplex
V-PLEX Proinflammatory Panel 1 Mouse Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, KC/GRO, TNF-α | Mouse
Multiplex
V-PLEX Rat IL-6 Kit
IL-6 | Rat
Singleplex
Proinflammatory Panel 1 Human Control Pack
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Proinflammatory Panel 1 Mouse Control Pack
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, KC/GRO, TNF-α | Mouse
Proinflammatory Panel 1 Rat Control Pack
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO, TNF-α | Rat
Human ProInflammatory-4 II Tissue Culture Kit
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
Human IL-6 Tissue Culture Kit
IL-6 | Human
Singleplex
Human ProInflammatory 7-Plex Tissue Culture Kit
IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, TNF-α | Human
Multiplex
Human ProInflammatory 9-Plex Tissue Culture Kit
GM-CSF, IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, TNF-α | Human
Multiplex
Human ProInflammatory-4 I Tissue Culture Kit
IFN-γ, IL-1β, IL-6, TNF-α | Human
Multiplex
Canine ProInflammatory Panel 3 Ultra-Sensitive Kit
IL-2, IL-6, IL-8, TNF-α | Canine
Multiplex
MA6000 Rat IL-6 384 Tissue Culture Kit
IL-6 | Rat
Singleplex
Mouse ProInflammatory 7-Plex Tissue Culture Kit
IFN-γ, IL-1β, IL-6, IL-10, IL-12p70, KC/GRO, TNF-α | Mouse
Multiplex
MA6000 Mouse IL-6 384 Tissue Culture Kit
IL-6 | Mouse
Singleplex
MS6000 Human ProInflammatory-4 II 384 Tissue Culture Kit
IL-6, IL-8 | Human
Multiplex
Mouse IL-6 Tissue Culture Kit
IL-6 | Mouse
Singleplex
V-PLEX Mouse Cytokine 29-Plex Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27p28/IL-30, IL-31, IL-33, IP-10, KC/GRO, MCP-1, MIP-1α, MIP-2, MIP-3α, TNF-α | Mouse
Multiplex
U-PLEX Biomarker Group 1 NHP Assays
CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17F, IL-18, IL-22, IL-23, IP-10, I-TAC, MCP-1, MCP-2, MCP-3, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TGF-β1, TGF-β2, TGF-β3, TNF-α, TNF-β, TPO, TRAIL, VEGF-A, YKL-40 | Non-human primate
MA6000 Human IL-6 384 Tissue Culture Kit
IL-6 | Human
Singleplex
V-PLEX Plus Mouse Cytokine 29-Plex Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27p28/IL-30, IL-31, IL-33, IP-10, KC/GRO, MCP-1, MIP-1α, MIP-2, MIP-3α, TNF-α | Mouse
Multiplex
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