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International Immunology, Vol. 11, No. 3, 471-480, March 1999
© 1999 Japanese Society for Immunology

IL-18-deficient mice are resistant to endotoxin-induced liver injury but highly susceptible to endotoxin shock

Yoshimitsu Sakao1,4, Kiyoshi Takeda1,4, Hiroko Tsutsui2,4, Tsuneyasu Kaisho1,3,4, Fumiko Nomura1,4, Haruki Okamura3,4, Kenji Nakanishi2,3,4 and Shizuo Akira1,3,4

1 Department of Biochemistry,
2 Department of Immunology and Medical Zoology, and
3 Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
4 CREST of Japan Science and Technology Corp.

Correspondence to: S. Akira

IL-18 is an IL-1-related cytokine which shares biological functions with IL-12. These include the activation of NK cells, induction of IFN-{gamma} production and Th1 cell differentiation. In this study we analyzed the effect of IL-18 deficiency on lipopolysaccharide (LPS)-induced liver injury and endotoxin shock in Propionibacterium acnes-primed mice. P. acnes-primed IL-18-deficient (IL-18KO) mice showed resistance to LPS-induced liver injury. Unexpectedly, P. acnes-primed IL-18KO mice were highly susceptible to LPS-induced endotoxin shock. Serum level of tumor necrosis factor (TNF)-{alpha} were markedly elevated (~10-fold higher) within 1.5 h after LPS challenge in IL-18KO mice as compared with wild-type mice. Anti-TNF-{alpha} antibody administration to IL-18KO mice was significantly protective against endotoxin-induced lethality. P. acnes-primed IL-18KO macrophages produced ~6-fold more TNF-{alpha} protein than did P. acnes-primed wild-type control macrophages. Taken together, these findings demonstrate that IL-18 is responsible for the progression of endotoxin-induced liver injury as well as down-regulation of endotoxin-induced TNF-{alpha} production in P. acnes-primed mice.

Keywords: endotoxin shock, IL-18, lipopolysaccharide, liver injury, tumor necrosis factor-{alpha}

Transmitting editor: K. Takatsu


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[Abstract] [Full Text] [PDF]

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Home page
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[Abstract] [Full Text] [PDF]

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Effect of interleukin-18 on mouse core body temperature
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2002; 282(3): R702 - R709.
[Abstract] [Full Text] [PDF]

Home page
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J. Immunol., November 15, 2001; 167(10): 5928 - 5934.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
C Hanck, T Manigold, U Bocker, M Kurimoto, C B Kolbel, M V Singer, and S Rossol
Gene expression of interleukin 18 in unstimulated peripheral blood mononuclear cells of patients with alcoholic cirrhosis
Gut, July 1, 2001; 49(1): 106 - 111.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

Home page
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[Full Text] [PDF]

Home page
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K.-i. Yamanaka, M. Tanaka, H. Tsutsui, T. S. Kupper, K. Asahi, H. Okamura, K. Nakanishi, M. Suzuki, N. Kayagaki, R. A. Black, et al.
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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