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Crit Care. 2007;11(6):R122.

Inhibition of the RAGE products increases survival in experimental models of severe sepsis and systemic infection.

Author information

1
Division of Infectious Diseases, Memorial Hospital of Rhode Island, 111 Brewster St, Pawtucket, RI 02860, USA.

Abstract

INTRODUCTION:

The receptor for advanced glycation end products (RAGE), a multi-ligand member of the immunoglobulin superfamily, contributes to acute and chronic disease processes, including sepsis.

METHODS:

We studied the possible therapeutic role of RAGE inhibition in the cecal ligation and puncture (CLP) model of polymicrobial sepsis and a model of systemic listeriosis using mice genetically deficient in RAGE expression or mice injected with a rat anti-murine RAGE monoclonal antibody.

RESULTS:

The 7-day survival rates after CLP were 80% for RAGE-/- mice (n = 15) (P < 0.01 versus wild-type), 69% for RAGE+/- mice (n = 23), and 37% for wild-type mice (n = 27). Survival benefits were evident in BALB/c mice given anti-RAGE antibody (n = 15 per group) over serum-treated control animals (P < 0.05). Moreover, delayed treatment with anti-RAGE antibody up to 24 hours after CLP resulted in a significant survival benefit compared with control mice. There was no significant increase in tissue colony counts from enteric Gram-negative or Gram-positive bacteria in animals treated with anti-RAGE antibody. RAGE-/-, RAGE+/-, and anti-RAGE antibody-treated animals were resistant to lethality from Listeria monocytogenes by almost two orders of magnitude compared with wild-type mice.

CONCLUSION:

Further studies are warranted to determine the clinical utility of anti-RAGE antibody as a novel treatment for sepsis.

PMID:
18042296
PMCID:
PMC2246216
DOI:
10.1186/cc6184
[Indexed for MEDLINE]
Free PMC Article

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