4.5 Article

Toll-like receptor-4 antagonist eritoran tetrasodium for severe sepsis

Journal

EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
Volume 9, Issue 5, Pages 507-520

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1586/ERI.11.27

Keywords

E5564; endotoxin; eritoran tetrasodium; sepsis; severe sepsis; TLR-4

Funding

  1. Eisai Medical Research
  2. Ferring Pharmaceuticals A/S
  3. Spectral Diagnostics, Inc.
  4. Pfizer Inc.
  5. Eisai Medical Research (eritoran)
  6. AstraZeneca (CytoFab)
  7. Agennix AG (talactoferrin)
  8. Artisan Pharma (recombinant soluble thrombomodulin)

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The human innate immune system initiates inflammation in response to bacterial molecules, particularly Gram-negative bacterial endotoxin. The steps by which endotoxin exposure leads to systemic inflammation include binding to Toll-like receptor-4 that specifically recognizes endotoxin and subsequently triggers cellular and molecular inflammatory responses. Severe sepsis is a systemic inflammatory response to infection that induces organ dysfunction and threatens a person's survival. Severe sepsis is frequently associated with increased blood levels of endotoxin. It is a significant medical problem that effects approximately 700,000 patients every year in the USA, resulting in 250,000 deaths. Eritoran tetrasodium is a nonpathogenic analog of bacterial endotoxin that antagonizes inflammatory signaling by the immune receptor Toll-like receptor-4. Eritoran is being evaluated for the treatment of patients with severe sepsis.

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