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Volume 2 Supplement 1

ESICM LIVES 2014

0093. Mitochondrial function of immune cells in severe sepsis and septic shock - a prospective observational cohort study

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Introduction

Circulating immune cells contribute to sepsis pathophysiology. Immune system activation increases cell energy requirements [1]; impaired mitochondrial function and ATP production may modulate the immune response in sepsis.

Objectives

To investigate mitochondrial enzyme activities and ATP content of monocytes, B cells and CD4+ T cells in patients with severe sepsis and septic shock.

Methods

30 patients with severe sepsis or septic shock were studied at ICU admission and after 24 and 48 hours. Immune cells were identified and isolated using an immunomagnetic positive cell isolation procedure (Dynabeads® for Human Monocytes, Human B cells, Human CD4 cells, Invitrogen Dynal AS, Oslo, Norway). Enzymatic activity of mitochondrial complexes I, IV, and ATP synthase and ATP content were measured spectrophotometrically and expressed as ratio to citrate synthase for enzymatic activities to account for mitochondrial mass and as mass per µg of cellular protein for ATP content. Maximal mitochondrial enzymatic activities and ATP in the first 48h of sepsis were compared with samples from 20 healthy volunteers (Mann Whitney test).

Results

Complex I and ATP synthase activities in sepsis were increased (p< 0.0001 to 0.0002; Figure 1, 2, 3). Complex IV activity was increased in monocytes (p=.0138). Complex IV activity in B and T cells was highly variable (Figures 1a-c). ATP content was increased in B cells but not in monocytes or T cell in sepsis compared to control. There were no differences between survivors and non-survivors in any of the enzymatic activities or in ATP content.

Figure 1
figure1

Maximal mitochondrial enzymatic activities and ATP content of human immune cells in the first 48h of sepsis : Monocytes

Figure 2
figure2

Maximal mitochondrial enzymatic activities and ATP content of human immune cells in the first 48h of sepsis: B cells

Figure 3
figure3

Maximal mitochondrial enzymatic activities and ATP content of human immune cells in the first 48h of sepsis: T cells

Conclusion

Mitochondrial enzyme activities of human immune cells are increased in severe sepsis and septic shock. We suggest that this helps to preserve normal or increased cell ATP content in acute inflammation.

References

  1. 1.

    Belikova I, et al.: Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis. Crit Care Med 2007,35(12):2702–2708.

  2. 2.

    Munoz C, et al.: Dysregulation of in vitro cytokine production by monocytes during sepsis. The Journal of clinical investigation 1991,88(5):1747–1754.

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GRANT ACKNOWLEDGEMENT

This study wass supported by Stiftung für die Forschung in Anästhesiologie und Intensivmedizin and the Gottfried und Julia Bangerter-Rhyner-Stiftung, both Bern, Switzerland.

Author information

Correspondence to TM Merz.

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Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Keywords

  • Immune Cell
  • Septic Shock
  • Severe Sepsis
  • Mitochondrial Function
  • Observational Cohort Study