Different efficacy of soluble CD14 treatment in high- and low-dose LPS models

F. Stelter, S. Witt, B. Fürll, R. S. Jack, Thomas Hartung, C. Schütt

Research output: Contribution to journalArticle

Abstract

Background: About 50% of septic shock cases are attributed to Gram- negative bacteria or their cell wall compound lipopolysaccharide (LPS, endotoxin). An attractive therapeutic strategy could target the binding of LPS to its cellular receptors. In vitro the soluble form of the endotoxin receptor CD14 (sCD14) competitively prevents binding of LPS to membrane- bound CD14 and inhibits LPS-stimulated macrophage responses. Methods: We tested the in vivo endotoxin-neutralizing capacity of human recombinant sCD14 using a mouse model of shock induced by 8μg g-1 of LPS from Salmonella abortus equi. Results: In this model, treatment with sCD14 reduced mortality if administered before or simultaneously with LPS. However, application of sCD 14 had no effect on the secretion of early proinflammatory cytokines and did not protect the animals against the development of apparent shock symptoms and liver injury. sCD14 also failed to prevent LPS-inducible (7-5 ng g-1) liver injury in galactosamine-sensitized mice. Conclusion: In line with these findings, sCD14 did not block LPS-induced activation of Kupffer cells in vitro, which might explain why the compound only partially protected in vivo.

Original languageEnglish (US)
Pages (from-to)205-213
Number of pages9
JournalEuropean Journal of Clinical Investigation
Volume28
Issue number3
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Endotoxins
Liver
Shock
Galactosamine
Salmonella
Kupffer Cells
Macrophages
Wounds and Injuries
Septic Shock
Gram-Negative Bacteria
Cell Wall
Lipopolysaccharides
Bacteria
Animals
Chemical activation
Cells
Cytokines
Membranes
Mortality
In Vitro Techniques

Keywords

  • CD 14
  • Kupffer cells
  • Lipopolysaccharide
  • Liver damage
  • Septic shock
  • Soluble CD14

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Different efficacy of soluble CD14 treatment in high- and low-dose LPS models. / Stelter, F.; Witt, S.; Fürll, B.; Jack, R. S.; Hartung, Thomas; Schütt, C.

In: European Journal of Clinical Investigation, Vol. 28, No. 3, 1998, p. 205-213.

Research output: Contribution to journalArticle

Stelter, F. ; Witt, S. ; Fürll, B. ; Jack, R. S. ; Hartung, Thomas ; Schütt, C. / Different efficacy of soluble CD14 treatment in high- and low-dose LPS models. In: European Journal of Clinical Investigation. 1998 ; Vol. 28, No. 3. pp. 205-213.
@article{a50dd5c9cd4f4cd3a648f883b0d3b988,
title = "Different efficacy of soluble CD14 treatment in high- and low-dose LPS models",
abstract = "Background: About 50{\%} of septic shock cases are attributed to Gram- negative bacteria or their cell wall compound lipopolysaccharide (LPS, endotoxin). An attractive therapeutic strategy could target the binding of LPS to its cellular receptors. In vitro the soluble form of the endotoxin receptor CD14 (sCD14) competitively prevents binding of LPS to membrane- bound CD14 and inhibits LPS-stimulated macrophage responses. Methods: We tested the in vivo endotoxin-neutralizing capacity of human recombinant sCD14 using a mouse model of shock induced by 8μg g-1 of LPS from Salmonella abortus equi. Results: In this model, treatment with sCD14 reduced mortality if administered before or simultaneously with LPS. However, application of sCD 14 had no effect on the secretion of early proinflammatory cytokines and did not protect the animals against the development of apparent shock symptoms and liver injury. sCD14 also failed to prevent LPS-inducible (7-5 ng g-1) liver injury in galactosamine-sensitized mice. Conclusion: In line with these findings, sCD14 did not block LPS-induced activation of Kupffer cells in vitro, which might explain why the compound only partially protected in vivo.",
keywords = "CD 14, Kupffer cells, Lipopolysaccharide, Liver damage, Septic shock, Soluble CD14",
author = "F. Stelter and S. Witt and B. F{\"u}rll and Jack, {R. S.} and Thomas Hartung and C. Sch{\"u}tt",
year = "1998",
doi = "10.1046/j.1365-2362.1998.00264.x",
language = "English (US)",
volume = "28",
pages = "205--213",
journal = "European Journal of Clinical Investigation",
issn = "0014-2972",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Different efficacy of soluble CD14 treatment in high- and low-dose LPS models

AU - Stelter, F.

AU - Witt, S.

AU - Fürll, B.

AU - Jack, R. S.

AU - Hartung, Thomas

AU - Schütt, C.

PY - 1998

Y1 - 1998

N2 - Background: About 50% of septic shock cases are attributed to Gram- negative bacteria or their cell wall compound lipopolysaccharide (LPS, endotoxin). An attractive therapeutic strategy could target the binding of LPS to its cellular receptors. In vitro the soluble form of the endotoxin receptor CD14 (sCD14) competitively prevents binding of LPS to membrane- bound CD14 and inhibits LPS-stimulated macrophage responses. Methods: We tested the in vivo endotoxin-neutralizing capacity of human recombinant sCD14 using a mouse model of shock induced by 8μg g-1 of LPS from Salmonella abortus equi. Results: In this model, treatment with sCD14 reduced mortality if administered before or simultaneously with LPS. However, application of sCD 14 had no effect on the secretion of early proinflammatory cytokines and did not protect the animals against the development of apparent shock symptoms and liver injury. sCD14 also failed to prevent LPS-inducible (7-5 ng g-1) liver injury in galactosamine-sensitized mice. Conclusion: In line with these findings, sCD14 did not block LPS-induced activation of Kupffer cells in vitro, which might explain why the compound only partially protected in vivo.

AB - Background: About 50% of septic shock cases are attributed to Gram- negative bacteria or their cell wall compound lipopolysaccharide (LPS, endotoxin). An attractive therapeutic strategy could target the binding of LPS to its cellular receptors. In vitro the soluble form of the endotoxin receptor CD14 (sCD14) competitively prevents binding of LPS to membrane- bound CD14 and inhibits LPS-stimulated macrophage responses. Methods: We tested the in vivo endotoxin-neutralizing capacity of human recombinant sCD14 using a mouse model of shock induced by 8μg g-1 of LPS from Salmonella abortus equi. Results: In this model, treatment with sCD14 reduced mortality if administered before or simultaneously with LPS. However, application of sCD 14 had no effect on the secretion of early proinflammatory cytokines and did not protect the animals against the development of apparent shock symptoms and liver injury. sCD14 also failed to prevent LPS-inducible (7-5 ng g-1) liver injury in galactosamine-sensitized mice. Conclusion: In line with these findings, sCD14 did not block LPS-induced activation of Kupffer cells in vitro, which might explain why the compound only partially protected in vivo.

KW - CD 14

KW - Kupffer cells

KW - Lipopolysaccharide

KW - Liver damage

KW - Septic shock

KW - Soluble CD14

UR - http://www.scopus.com/inward/record.url?scp=0031972411&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031972411&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2362.1998.00264.x

DO - 10.1046/j.1365-2362.1998.00264.x

M3 - Article

C2 - 9568466

AN - SCOPUS:0031972411

VL - 28

SP - 205

EP - 213

JO - European Journal of Clinical Investigation

JF - European Journal of Clinical Investigation

SN - 0014-2972

IS - 3

ER -