Jang 2019 Crit Care Med

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Jang D, Hallisey S, Zhou V, Owiredu S, Shofer F, Greenwood J, Eckmann D (2019) Changes in inflammataion and mitochondrial function in blood cells obtained from patients with sepsis. Crit Care Med.

Link: Open Access

Jang D, Hallisey S, Zhou V, Owiredu S, Shofer F, Greenwood J, Eckmann D (2019)

Event: Crit Care Med

Mitochondrial dysfunction and inflammation has been identified as an important cellular event leading to end organ dysfunction in sepsis. We evaluated alterations in respiration, mitochondrial movement and biomarkers of inflammation (IL-6, IL-10, and TNF) in plasma and peripheral blood mononuclear cells (PBMCs) obtained from patients with sepsis and healthy controls.

This is an ongoing prospective observational study in a single site academic emergency department comparing mitochondrial function and inflammation in two groups: Sepsis (includes sepsis and septic shock) and Controls (healthy subjects). PBMCs from subjects in the Sepsis and Control group were analyzed with high-resolution respirometry (Oroboros O2k) to obtain cellular respiration and mitochondrial movement with fluorescence microscopy. Plasma from both groups was used to measure biomarkers of inflammation with digital ELISA (Simoa) to obtain concentrations of IL-6, IL-10, and TNF.

We enrolled 16 subjects (6 in the Sepsis group and 10 healthy subjects in the Control group for comparison). In the Sepsis group the mean age (SD) was 65.5+/-3; 50% male; In-hospital mortality was 33%. Mean initial SOFA score was 7 +/-3.45. Mean lactate on presentation was 2.95+/-0.28. PMBCs obtained from subjects in the Sepsis group had overall significantly lower respiration and increased H2O2 production compared to the Control group (P < 0.05). There was an overall increase in net movement of mitochondria within PBMCs in the Sepsis group (310+/- 12 nm) when compared to the Control group (189+/-11 nm). The following mean concentration (pg/mL) of biomarkers of inflammation measured in the Sepsis group compared to controls, respectively: IL-6 (48.5+/-38.9 versus 0.25+/-0.08, P = 0.02); IL-10 (57.7+/-92.9 versus 0.13+/-0.29, P = 0.11); TNF (13.2+/-12.2 versus 1.01+/-0.47, P = 0.91).

In this study, PBMCs obtained from subjects in Sepsis group had significantly lower respiration, increased H2O2 production and increased mitochondrial movement when compared to the Control group. We also measured biomarkers of inflammation in both groups, and while there were higher concentrations in the Sepsis group, there was no statistical significance. The study findings demonstrate alterations in mitochondrial function in human blood cells that could be used as a potential biomarker of disease severity.


Bioblast editor: Plangger M


Affiliations

Jang D(1,2), Hallisey S(2), Zhou V(3), Owiredu S(4), Shofer F(2), Greenwood J(2), Eckmann D(4)

  1. N/A, Philadelphia, PA,
  2. Univ Pennsylvania, Philadelphia, PA,
  3. Univ Rochester, Rochester, NY,
  4. Univ Pennsylvania Health System, Philadelphia, PA


Labels: MiParea: Respiration  Pathology: Sepsis 


Tissue;cell: Blood cells 



HRR: Oxygraph-2k 

PBMC