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Advances in understanding sepsis

Published online by Cambridge University Press:  01 February 2008

M. Shimaoka  and
E. J. Park
M. Shimaoka*
Affiliation:
Harvard Medical School, The CBR Institute for Biomedical Research, Department of Anesthesia, Boston, MA, USA
E. J. Park
Affiliation:
Harvard Medical School, The CBR Institute for Biomedical Research, Department of Anesthesia, Boston, MA, USA
*
Correspondence to: Motomu Shimaoka, The CBR Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Room 253, Boston, MA 02115, USA. E-mail: [email protected]; Tel: +1 617 278 3272; Fax: +1 617 278 3232
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Summary

Sepsis, a systemic inflammatory response to infection, is a leading cause of death in intensive care units. Recent investigations into the pathogenesis of sepsis reveal a biphasic inflammatory process. An early phase is characterized by pro-inflammatory cytokines (e.g. tumour necrosis factor-α), whereas a late phase is mediated by an inflammatory high-mobility group box 1 and an anti-inflammatory interleukin-10. Inflammation aberrantly activates coagulation cascades as sepsis progresses. This dual inflammatory response concomitant with dysregulated coagulation partially accounts for unsuccessful anti-cytokine therapies that have solely targeted early pro-inflammatory mediators (e.g. tumour necrosis factor-α). In contrast, activated protein C, which modifies both inflammatory and coagulatory pathways, has improved survival in patients in severe sepsis. Inhibition of the late mediator high-mobility group box 1 improves survival in established sepsis in pre-clinical studies. In addition, recent advances in molecular medicine have shed light on two novel experimental interventions against sepsis. Accelerated apoptosis of lymphocytes has been shown to play an important role in organ dysfunction in sepsis and techniques to suppress apoptosis have improved survival rate in sepsis models. The vagus nerve system has also been shown to suppress innate immune response through endogenous release and exogenous administration of cholinergic agonists, ameliorating inflammation and lethality in sepsis models.

Keywords

SEPSISINFLAMMATIONAPOPTOSISCOAGULATIONIMMUNOSUPRESSIONCHOLINERGIC FIBRES
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue S42 , February 2008 , pp. 146 - 153
Copyright
Copyright © European Society of Anaesthesiology 2008

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