Sepsis

Links between pathogen sensing and organ damage

Elliott Crouser, Matthew Exline, Daren L Knoell, Mark D. Wewers

Research output: Contribution to journalReview article

30 Citations (Scopus)

Abstract

The host's inflammatory response to sepsis can be divided into two phases, the initial detection and response to the pathogen initiated by the innate immune response, and the persistent inflammatory state characterized by multiple organ dysfunction syndrome (MODS). New therapies aimed at pathogen recognition receptors (PRRs) particularly the TLRs and the NOD-like receptors offer hope to suppress the initial inflammatory response in early sepsis and to bolster this response in late sepsis. The persistence of MODS after the initial inflammatory surge can also be a determining factor to host survival. MODS is due to the cellular damage and death induced by sepsis. The mechanism of this cell death depends in part upon mitochondrial dysfunction. Damaged mitochondria have increased membrane permeability prompting their autophagic removal if few mitochondria are involved but apoptotic cell death may occur if the mitochondrial losses are more extensive. In addition severe loss of mitochondria results in low cell energy stores, necrotic cell death, and increased inflammation driven by the release of cell components such as HMGB1. Therapies, which aim at improving cellular energy reserves such as the promotion of mitochondrial biogenesis by insulin, may have a role in future sepsis therapies. Finally, both the inflammatory responses and the susceptibility to organ failure may be modulated by nutritional status and micronutrients, such as zinc, Therapies aimed at micronutrient repletion may further augment approaches targeting PRR function and mitochondrial viability.

Original languageEnglish (US)
Pages (from-to)1840-1852
Number of pages13
JournalCurrent Pharmaceutical Design
Volume14
Issue number19
DOIs
StatePublished - Jul 1 2008

Fingerprint

Sepsis
Multiple Organ Failure
Mitochondria
Cell Death
Micronutrients
HMGB1 Protein
Organelle Biogenesis
Cellular Structures
Therapeutics
Nutritional Status
Innate Immunity
Zinc
Permeability
Insulin
Inflammation
Membranes

Keywords

  • Biogenesis
  • Inflammation
  • Mitochondria
  • Multiple organ dysfunction syndrome (MODS)
  • Necrotic cell death
  • Pathogen
  • Pathogen recognition receptors (PRRs)
  • Sepsis

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Sepsis : Links between pathogen sensing and organ damage. / Crouser, Elliott; Exline, Matthew; Knoell, Daren L; Wewers, Mark D.

In: Current Pharmaceutical Design, Vol. 14, No. 19, 01.07.2008, p. 1840-1852.

Research output: Contribution to journalReview article

Crouser, Elliott ; Exline, Matthew ; Knoell, Daren L ; Wewers, Mark D. / Sepsis : Links between pathogen sensing and organ damage. In: Current Pharmaceutical Design. 2008 ; Vol. 14, No. 19. pp. 1840-1852.
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