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Mechanisms in Patients and Volunteers
Monocyte deactivation is associated with immunosuppression in sepsis. Le Tulzo and coworkers examined class II molecule human leukocyte antigen (HLA)-DR expression on circulating monocytes in 48 patients with sepsis using flow cytometry. Persistently lowered expression at Day 6 correlated with severity scores, secondary infection, and death. This phenomenon occurred at a transcriptional level via a decrease in the class II transactivator A (CIITA) transcription. These abnormalities correlated with high cortisol levels observed in sepsis and not with those of other factors, such as catecholamines or IL-10. In in vitro studies, glucocorticoids decreased HLA-DR expression at a transcriptional level via a decrease in CIITA mRNA levels, mainly by downmodulating isoforms I and III. The authors concluded that, in human sepsis, the loss of HLA-DR expression on circulating monocytes is associated with poor outcome and that high endogenous cortisol levels are possibly involved in the loss of HLA-DR expression on monocytes via effects on HLA-DR and CIITA transcription.
The transcriptional regulatory factor, nuclear factor- B, modulates many of the proinflammatory mediators implicated in acute lung injury. In 30 patients with acute lung injury, Yang and coworkers
examined the relationship between clinical outcome and activation of nuclear factor-B in peripheral neutrophils. Nuclear translocation of nuclear factor-B depended on activation of p38 mitogen-activated protein and Akt kinases. Diminished activation of nuclear factor-B or Akt, but not p38 mitogen-activated protein, in the early period after intubation was associated with a shorter duration of mechanical ventilation and improved survival. The authors conclude that alterations in neutrophil activation patterns in patients with early acute lung injury, particularly involving the ability to accumulate nuclear factor-B in the nucleus after relevant stimuli, influences subsequent clinical course.
In a clinical commentary, Vieillard-Baron and colleagues
discuss the use of echocardiography in assessing hemodynamic instability in sepsis.
Citations 1-3 of 3 total displayed.
Monocyte Human Leukocyte Antigen–DR Transcriptional Downregulation by Cortisol during Septic Shock
- Yves Le Tulzo, Celine Pangault, Laurence Amiot, Valérie Guilloux, Olivier Tribut, Cédric Arvieux, Christophe Camus, Renée Fauchet, Rémi Thomas, and Bernard Drénou
Am. J. Respir. Crit. Care Med. 169: 1144 -1151. First published online as doi:10.1164/rccm.200309-1329OC
[Abstract]
[Full text]
Hemodynamic Instability in Sepsis: Bedside Assessment by Doppler Echocardiography
- Antoine Vieillard-Baron, Sebastien Prin, Karim Chergui, Olivier Dubourg, and François Jardin
Am. J. Respir. Crit. Care Med. 168: 1270-1276.
[Full text]
Early Alterations in Neutrophil Activation Are Associated with Outcome in Acute Lung Injury
- Kuang-Yao Yang, John J. Arcaroli, and Edward Abraham
Am. J. Respir. Crit. Care Med. 167: 1567 -1574. First published online as doi:10.1164/rccm.200207-664OC
[Abstract]
[Full text]
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