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Type I interferon drives tumor necrosis factor-induced lethal shock

(2009) JOURNAL OF EXPERIMENTAL MEDICINE. 206(9). p.1873-1882
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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.
Keywords
CELLS, IDENTIFICATION, ALPHA, RECEPTOR, INHIBITION, APOPTOSIS, TNF, RECOMBINANT HUMAN, TRANSCRIPTION, MICE

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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.
@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},
}

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