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Type I interferon drives tumor necrosis factor-induced lethal shock

LIESBETH HUYS UGent, Filip Van Hauwermeiren UGent, Lien Dejager UGent, Eline Dejonckheere UGent, Stefan Lienenklaus, Siegfried Weiss, Georges Leclercq UGent and Claude Libert UGent (2009) JOURNAL OF EXPERIMENTAL MEDICINE. 206(9). p.1873-1882
abstract
Tumor necrosis factor (TNF) is reputed to have very powerful antitumor effects, but it is also a strong proinflammatory cytokine. Injection of TNF in humans and mice leads to a systemic inflammatory response syndrome with major effects on liver and bowels. TNF is also a central mediator in several inflammatory diseases. We report that type I interferons (IFNs) are essential mediators of the lethal response to TNF. Mice deficient in the IFN-alpha receptor 1 (IFNAR-1) or in IFN-beta are remarkably resistant to TNF-induced hypothermia and death. After TNF injection, IFNAR-1-/- mice produced less IL-6, had less bowel damage, and had less apoptosis of enterocytes and hepatocytes compared with wild-type (WT) mice. Extensive gene expression analysis in livers of WT and IFNAR-1-/- mice revealed a large deficiency in the response to TNF in the knockout mice, especially of IFN-stimulated response element–dependent genes, many of which encode chemokines. In livers of IFNAR-1-/- mice, fewer infiltrating white blood cells (WBCs) were detected by immunohistochemistry. Deficiency of type I IFN signaling provided sufficient protection for potentially safer therapeutic use of TNF in tumor-bearing mice. Our data illustrate that type I IFNs act as essential mediators in TNF-induced lethal inflammatory shock, possibly by enhancing cell death and inducing chemokines and WBC infiltration in tissues.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
CELLS, IDENTIFICATION, ALPHA, RECEPTOR, INHIBITION, APOPTOSIS, TNF, RECOMBINANT HUMAN, TRANSCRIPTION, MICE
journal title
JOURNAL OF EXPERIMENTAL MEDICINE
J. Exp. Med.
volume
206
issue
9
pages
1873 - 1882
Web of Science type
Article
Web of Science id
000269439000006
JCR category
MEDICINE, RESEARCH & EXPERIMENTAL
JCR impact factor
14.505 (2009)
JCR rank
3/90 (2009)
JCR quartile
1 (2009)
ISSN
0022-1007
DOI
10.1084/jem.20090213
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
787863
handle
http://hdl.handle.net/1854/LU-787863
date created
2009-11-23 16:44:50
date last changed
2012-06-26 14:31:49
@article{787863,
  abstract     = {Tumor necrosis factor (TNF) is reputed to have very powerful antitumor effects, but it is also a strong proinflammatory cytokine. Injection of TNF in humans and mice leads to a systemic inflammatory response syndrome with major effects on liver and bowels. TNF is also a central mediator in several inflammatory diseases. We report that type I interferons (IFNs) are essential mediators of the lethal response to TNF. Mice deficient in the IFN-alpha receptor 1 (IFNAR-1) or in IFN-beta are remarkably resistant to TNF-induced hypothermia and death. After TNF injection, IFNAR-1-/- mice produced less IL-6, had less bowel damage, and had less apoptosis of enterocytes and hepatocytes compared with wild-type (WT) mice. Extensive gene expression analysis in livers of WT and IFNAR-1-/-  mice revealed a large deficiency in the response to TNF in the knockout mice, especially of IFN-stimulated response element--dependent genes, many of which encode chemokines. In livers of IFNAR-1-/-  mice, fewer infiltrating white blood cells (WBCs) were detected by immunohistochemistry. Deficiency of type I IFN signaling provided sufficient protection for potentially safer therapeutic use of TNF in tumor-bearing mice. Our data illustrate that type I IFNs act as essential mediators in TNF-induced lethal inflammatory shock, possibly by enhancing cell death and inducing chemokines and WBC infiltration in tissues.},
  author       = {HUYS, LIESBETH and Van Hauwermeiren, Filip and Dejager, Lien and Dejonckheere, Eline and Lienenklaus, Stefan and Weiss, Siegfried and Leclercq, Georges and Libert, Claude},
  issn         = {0022-1007},
  journal      = {JOURNAL OF EXPERIMENTAL MEDICINE},
  keyword      = {CELLS,IDENTIFICATION,ALPHA,RECEPTOR,INHIBITION,APOPTOSIS,TNF,RECOMBINANT HUMAN,TRANSCRIPTION,MICE},
  language     = {eng},
  number       = {9},
  pages        = {1873--1882},
  title        = {Type I interferon drives tumor necrosis factor-induced lethal shock},
  url          = {http://dx.doi.org/10.1084/jem.20090213},
  volume       = {206},
  year         = {2009},
}

Chicago
HUYS, LIESBETH, Filip Van Hauwermeiren, Lien Dejager, Eline Dejonckheere, Stefan Lienenklaus, Siegfried Weiss, Georges Leclercq, and Claude Libert. 2009. “Type I Interferon Drives Tumor Necrosis Factor-induced Lethal Shock.” Journal of Experimental Medicine 206 (9): 1873–1882.
APA
HUYS, L., Van Hauwermeiren, F., Dejager, L., Dejonckheere, E., Lienenklaus, S., Weiss, S., Leclercq, G., et al. (2009). Type I interferon drives tumor necrosis factor-induced lethal shock. JOURNAL OF EXPERIMENTAL MEDICINE, 206(9), 1873–1882.
Vancouver
1.
HUYS L, Van Hauwermeiren F, Dejager L, Dejonckheere E, Lienenklaus S, Weiss S, et al. Type I interferon drives tumor necrosis factor-induced lethal shock. JOURNAL OF EXPERIMENTAL MEDICINE. 2009;206(9):1873–82.
MLA
HUYS, LIESBETH, Filip Van Hauwermeiren, Lien Dejager, et al. “Type I Interferon Drives Tumor Necrosis Factor-induced Lethal Shock.” JOURNAL OF EXPERIMENTAL MEDICINE 206.9 (2009): 1873–1882. Print.