Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis

  title={Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis},
  author={Shih-Chin Cheng and Brendon P. Scicluna and Rob J W Arts and Mark S Gresnigt and Ekta Lachmandas and Evangelos J Giamarellos-Bourboulis and Matthijs Kox and Ganesh R. Manjeri and Jori A. L. Wagenaars and Olaf L. Cremer and Jenneke Leentjens and Anne Jan van der Meer and Frank L van de Veerdonk and Marc Bonten and Marcus J. Schultz and Peter H G M Willems and Peter Pickkers and Leo A B Joosten and Tom van der Poll and Mihai G Netea},
  journal={Nature Immunology},
The acute phase of sepsis is characterized by a strong inflammatory reaction. At later stages in some patients, immunoparalysis may be encountered, which is associated with a poor outcome. By transcriptional and metabolic profiling of human patients with sepsis, we found that a shift from oxidative phosphorylation to aerobic glycolysis was an important component of initial activation of host defense. Blocking metabolic pathways with metformin diminished cytokine production and increased… CONTINUE READING
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