Format

Send to

Choose Destination
See comment in PubMed Commons below
J Infect Dis. 2012 Feb 1;205(3):392-400. doi: 10.1093/infdis/jir764. Epub 2011 Dec 16.

The effects of sepsis on mitochondria.

Author information

1
Mitochondrial Research Laboratory, IDIBAPS, University of Barcelona, Internal Medicine Department, Hospital Clínic of Barcelona (HCB, Barcelona) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Valencia). garrabou@clinic.ub.es

Abstract

BACKGROUND:

Sepsis is associated with mitochondrial dysfunction and impaired oxygen consumption, which may condition clinical outcome independent of tissue oxygenation. However, mitochondrial role in sepsis severity remains unknown. We aimed to characterize mitochondrial function in sepsis, establish its origin and cellular consequences, and determine its correlation with clinical symptoms and outcome.

METHODS:

Different markers of mitochondrial activity, nitrosative and oxidative stress, apoptosis, and inflammation were measured in peripheral blood mononuclear cells (PBMCs) and plasma of 19 septic patients and 20 controls. Plasma capacity to induce mitochondrial dysfunction was assessed in muscle mitochondria from 5 healthy individuals incubated with plasma of septic patients or controls.

RESULTS:

Despite unaltered mitochondrial mass and protein synthesis, enzymatic mitochondrial complexes I, III, and IV and oxygen consumption were significantly inhibited in sepsis. Septic plasma tended to reduce oxygen consumption of healthy mitochondria and showed significantly increased amounts of extracellular mitochondrial DNA and inflammatory cytokines, especially in patients presenting adverse outcome. Active nuclear factor kappa-light-chain enhancer of activated B cells (NFKB) was also significantly increased, together with nitric oxide, oxidative stress and apoptosis. Additionally, sepsis severity significantly correlated with complex I inhibition, NFKB activation and intercellular adhesion molecule expression.

CONCLUSIONS:

A plasmatic factor such as nitric oxide, increased in inflammation and able to induce mitochondrial dysfunction, oxidative stress and apoptosis, may be responsible for cell damage in sepsis. Together with bacterial infection, leakage of mitochondrial DNA from damaged cells into circulation could contribute to systemic inflammatory response syndrome. Mitochondrial dysfunction and inflammation correlate with sepsis severity and outcome, becoming targets for supporting therapies.

PMID:
22180620
DOI:
10.1093/infdis/jir764
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems
    Loading ...
    Support Center