Cheng 2016 Nat Immunol: Difference between revisions
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{{Publication | {{Publication | ||
|title=Cheng SC, Scicluna BP, Arts RJ, Gresnigt MS, Lachmandas E, Giamarellos-Bourboulis EJ, Kox M, Manjeri GR, Wagenaars JA, Cremer OL, Leentjens J, van der Meer AJ, van de Veerdonk FL, Bonten MJ, Schultz MJ, Willems PH, Pickkers P, Joosten LA, van der Poll T, Netea MG (2016) Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis. Nat Immunol 17:406-13. ย | |title=Cheng SC, Scicluna BP, Arts RJ, Gresnigt MS, Lachmandas E, Giamarellos-Bourboulis EJ, Kox M, Manjeri GR, Wagenaars JA, Cremer OL, Leentjens J, van der Meer AJ, van de Veerdonk FL, Bonten MJ, Schultz MJ, Willems PH, Pickkers P, Joosten LA, van der Poll T, Netea MG (2016) Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis. Nat Immunol 17:406-13. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/26950237 PMID: 26950237] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/26950237 PMID: 26950237] | ||
|authors=Cheng SC, Scicluna BP, Arts RJ, Gresnigt MS, Lachmandas E, Giamarellos-Bourboulis EJ, Kox M, Manjeri GR, Wagenaars JA, Cremer OL, Leentjens J, van der Meer AJ, van de Veerdonk FL, Bonten MJ, Schultz MJ, Willems PH, Pickkers P, Joosten LA, van der Poll T, Netea MG | |authors=Cheng SC, Scicluna BP, Arts RJ, Gresnigt MS, Lachmandas E, Giamarellos-Bourboulis EJ, Kox M, Manjeri GR, Wagenaars JA, Cremer OL, Leentjens J, van der Meer AJ, van de Veerdonk FL, Bonten MJ, Schultz MJ, Willems PH, Pickkers P, Joosten LA, van der Poll T, Netea MG | ||
| Line 6: | Line 6: | ||
|journal=Nat Immunol | |journal=Nat Immunol | ||
|abstract=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 mortality in systemic fungal infection in mice. In contrast, in leukocytes rendered tolerant by exposure to lipopolysaccharide or after isolation from patients with sepsis and immunoparalysis, a generalized metabolic defect at the level of both glycolysis and oxidative metabolism was apparent, which was restored after recovery of the patients. Finally, the immunometabolic defects in humans were partially restored by therapy with recombinant interferon-ฮณ, which suggested that metabolic processes might represent a therapeutic target in sepsis. | |abstract=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 mortality in systemic fungal infection in mice. In contrast, in leukocytes rendered tolerant by exposure to lipopolysaccharide or after isolation from patients with sepsis and immunoparalysis, a generalized metabolic defect at the level of both glycolysis and oxidative metabolism was apparent, which was restored after recovery of the patients. Finally, the immunometabolic defects in humans were partially restored by therapy with recombinant interferon-ฮณ, which suggested that metabolic processes might represent a therapeutic target in sepsis. | ||
|keywords=PBMC, Warburg effect | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, Patients, Pharmacology;toxicology | |area=Respiration, mt-Medicine, Patients, Pharmacology;toxicology | ||
|organism=Human | |organism=Human | ||
|tissues=Blood cells | |tissues=Blood cells | ||
|model cell lines=Lymphocyte | |||
|preparations=Intact cells | |preparations=Intact cells | ||
|diseases=Sepsis | |diseases=Sepsis | ||
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|substratestates=ROX | |substratestates=ROX | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional= | |additional=2016-06 | ||
}} | }} | ||
Revision as of 13:17, 9 September 2016
| Cheng SC, Scicluna BP, Arts RJ, Gresnigt MS, Lachmandas E, Giamarellos-Bourboulis EJ, Kox M, Manjeri GR, Wagenaars JA, Cremer OL, Leentjens J, van der Meer AJ, van de Veerdonk FL, Bonten MJ, Schultz MJ, Willems PH, Pickkers P, Joosten LA, van der Poll T, Netea MG (2016) Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis. Nat Immunol 17:406-13. |
Cheng SC, Scicluna BP, Arts RJ, Gresnigt MS, Lachmandas E, Giamarellos-Bourboulis EJ, Kox M, Manjeri GR, Wagenaars JA, Cremer OL, Leentjens J, van der Meer AJ, van de Veerdonk FL, Bonten MJ, Schultz MJ, Willems PH, Pickkers P, Joosten LA, van der Poll T, Netea MG (2016) Nat Immunol
Abstract: 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 mortality in systemic fungal infection in mice. In contrast, in leukocytes rendered tolerant by exposure to lipopolysaccharide or after isolation from patients with sepsis and immunoparalysis, a generalized metabolic defect at the level of both glycolysis and oxidative metabolism was apparent, which was restored after recovery of the patients. Finally, the immunometabolic defects in humans were partially restored by therapy with recombinant interferon-ฮณ, which suggested that metabolic processes might represent a therapeutic target in sepsis. โข Keywords: PBMC, Warburg effect
Labels: MiParea: Respiration, mt-Medicine, Patients, Pharmacology;toxicology
Pathology: Sepsis
Organism: Human Tissue;cell: Blood cells Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k
2016-06
