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Intensive Care Medicine

, Volume 36, Issue 6, pp 956–962 | Cite as

Fall in circulating mononuclear cell mitochondrial DNA content in human sepsis

  • Angela Pyle
  • David J. Burn
  • Charlotte Gordon
  • Catherine Swan
  • Patrick F. ChinneryEmail author
  • Simon V. Baudouin
Original

Abstract

Purpose

Loss of mitochondrial DNA (mtDNA) has been described in whole blood samples from a small number of patients with sepsis, but the underlying mechanism and clinical implications of this observation are not clear. We have investigated the cellular basis of the mtDNA depletion in sepsis, and determined clinical correlates with mtDNA depletion.

Methods

Whole blood samples were obtained from 147 consecutive patients with severe sepsis admitted to a General Critical Care Unit in a University Hospital and 83 healthy controls. In a separate study of 13 patients with severe sepsis, blood was obtained for immediate cell sorting by flow cytometry. MtDNA content was determined in whole blood DNA by PCR methods, and subsequently in the 13 samples where white cell subtypes were separated.

Results

The mtDNA content of peripheral blood in human subjects was lower in patients with sepsis than controls (P < 0.0001). By studying leukocyte subsets in a subgroup of 13 patients, we showed that this was largely due to an increase in the proportion of circulating neutrophils, which contained ~3-fold less mtDNA than mononuclear leukocytes. However, isolated monocytes (P = 0.041) and lymphocytes (P = 0.021) from septic patients showed clear evidence of mtDNA depletion, which correlated with the APACHE II score (P = 0.015).

Conclusions

In severe sepsis much of the apparent whole blood mtDNA depletion is due to a change in the differential leukocyte count. However mtDNA depletion in mononuclear cells occurs in patients with sepsis and correlates with disease severity.

Keywords

Sepsis Mitochondria Copy number Neutrophil Monocyte Lymphocyte 

Notes

Acknowledgments

PFC is a Wellcome Trust Senior Fellow in Clinical Science who also receives funding from the EU FP6 program, EUmitocombat and MITOCIRCLE, the Parkinson's Disease Society (UK) and the Medical Research Council (UK). We thank Ian Dimmick and Rebecca Stewart for their assistance with the flow cytometry experiments. This work was principally funded by an unconditional research grant from the United States Army.

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Copyright information

© Copyright jointly held by Springer and ESICM 2010

Authors and Affiliations

  • Angela Pyle
    • 1
  • David J. Burn
    • 2
  • Charlotte Gordon
    • 3
    • 4
  • Catherine Swan
    • 3
    • 4
  • Patrick F. Chinnery
    • 1
    Email author
  • Simon V. Baudouin
    • 3
    • 4
  1. 1.Mitochondrial Research Group, Institute for Ageing and Health, The Medical SchoolNewcastle UniversityNewcastleUK
  2. 2.Clinical Ageing Research Unit, Institute for Ageing and Health, The Medical SchoolNewcastle UniversityNewcastleUK
  3. 3.Institute of Cellular MedicineNewcastle UniversityNewcastleUK
  4. 4.Critical Care Unit, Royal Victoria InfirmaryNewcastleUK

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