Involvement of IL-18 and Soluble Fas in Patients with Postoperative Hepatic FailureNakae H.a · Zheng Y.-J.a · Wada H.a · Tajimi K.a · Endo S.b
aDepartment of Emergency and Critical Care Medicine, Akita University School of Medicine, Akita, and bDepartment of Critical Care Medicine, Iwate University School of Medicine, Morioka, Japan
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
We measured the levels of tumor necrosis factor alpha (TNF-α), interleukins (IL)-6 and -18, and soluble Fas (sFas) in 11 patients with postoperative hepatic failure and assessed whether IL-18-mediated apoptosis is involved in the onset of liver dysfunction. The serum TNF-α, IL-18, and sFas levels were significantly higher in patients with sepsis as a complication than in those without sepsis. The TNF-α and IL-18 levels were significantly higher in nonsurvivors than in survivors. Significant correlations were observed between TNF-α and IL-6, between TNF-α and IL-18, and between TNF-α and sFas levels. These results showed that Fas-mediated hepatocyte apoptosis functions as an important mechanism responsible for the onset of postoperative hepatic failure in humans. They especially suggested that IL-18 and TNF-α function both as apoptosis-promoting factors and as apoptosis-inhibiting factors, depending on the conditions to which hepatocytes are subjected.
© 2003 S. Karger AG, Basel
- Galle PR, Hofmann WJ, Walczak H, Schaller H, Otto G, Stremmel W, Krammer PH, Runkel L: Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage. J Exp Med 1995;182:1223–1230.
- Ogasawara J, Watanabe-Fukunaga R, Adachi M, Matsuzawa A, Kasugai T, Kitamura Y, Itoh N, Suda T, Nagata S: Lethal effect of the anti-Fas antibody in mice. Nature 1993;364:806–809.
- Watanabe-Fukunaga R, Brannan CI, Itoh N, Yonehara S, Copeland NG, Jenkins NA, Nagata S: The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen. J Immunol 1992;148:1274–1279.
- Kägi D, Vignaux F, Ledermann B, Bürki K, Depraetere V, Nagata S, Hengartner H, Golstein P: Fas and perforin pathways as major mechanisms of T-cell-mediated cytotoxicity. Science 1994;265:528–530.
- Lowin B, Hahne M, Mattmann C, Tschopp J: Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature 1994;370:650–652.
- Suda T, Okazaki T, Naito Y, Yokota T, Arai N, Ozaki S, Nakao K, Nagata S: Expression of the Fas ligand in cells of T cell lineage. J Immunol 1995;154:3806–3813.
- Leist M, Gantner F, Bohlinger L, Tiegs G, Germann PG, Wendel A: Tumor necrosis factor-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models. Am J Pathol 1995;146:1220–1223.
- Ni R, Tomita Y, Matsuda K, Ichihara A, Ishimura K, Ogasawara J, Nagata S: Fas-mediated apoptosis in primary cultured mouse hepatocytes. Exp Cell Res 1994;215:332–337.
- Shinagawa T, Yoshioka K, Kakumu S, Wakita T, Ishikawa T, Itoh Y, Takayanagi M: Apoptosis in cultured rat hepatocytes: The effects of tumour necrosis factor alpha and interferon gamma. J Pathol 1991;165:247–253.
- Kondo T, Suda T, Fukuyama H, Adachi M, Nagata S: Essential roles of the Fas ligand in the development of hepatitis. Nat Med 1997;3:409–413.
- Nakae H, Narita K, Endo S: Soluble Fas and soluble Fas ligand levels in patients with acute hepatic failure. J Crit Care 2001;16:59–63.
- Nakae H, Yonekawa C, Narita K, Endo S: Are proinflammatory cytokine concentrations reduced by plasma exchange in patients with severe acute hepatic failure? Res Commun Mol Pathol Pharmacol 2001;109:65–72.
- Nakae H, Yonekawa C, Wada H, Asanuma Y, Sato T, Tanaka H: Effectiveness of combining plasma exchange and continuous hemodiafiltration (combined modality therapy in a parallel circuit) in the treatment of patients with acute hepatic failure. Ther Apher 2001;5:471–475.
- Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K: Cloning of a new cytokine that induces IFN-γ production by T cells. Nature 1995;378:88–91.
- Tsutsui H, Matsui K, Kawada N, Hyodo Y, Hayashi N, Okamura H, Higashino K, Nakanishi K: IL-18 accounts for both TNF-α and Fas ligand-mediated hepatotoxic pathways in endotoxin-induced liver injury in mice. J Immunol 1997;159:3961–3967.
- Tsutsui H, Nakanishi K, Matsui K, Higashino K, Okamura H, Miyazawa Y, Kaneda K: IFN-γ-inducing factor up-regulates Fas ligand-mediated cytotoxic activity of murine natural killer cell clones. J Immunol 1996;157:3967–3973.
- Matsubara S, Okabe K, Ouchi K, Miyazaki Y, Yajima Y, Suzuki H, Otsuki M, Matsuno S: Continuous removal of middle molecules by hemofiltration in patients with acute liver failure. Crit Care Med 1990;18:1331–1338.
- Sekiyama KD, Yoshiba M, Thomson AW: Circulating proinflammatory cytokines (IL-1β, TNF-α, and IL-6) and IL-1 receptor antagonist (IL-1Ra) in fulminant hepatic failure and acute hepatitis. Clin Exp Immunol 1994;98:71–77.
- American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864–874.
Sheron N, Goka J, Wendon J: Highly elevated plasma cytokines in fulminant hepatic failure: Correlation with multi-organ failure and death (abstract). Hepatology 1990;12:939.
- Colletti LM, Cortis A, Lukacs N, Kunkel SL, Green M, Strieter RM: Tumor necrosis factor up-regulates intercellular adhesion molecule 1, which is important in the neutrophil-dependent lung and liver injury associated with hepatic ischemia and reperfusion in the rat. Shock 1998;10:182–191.
- Sato T, Asanuma Y, Masaki Y, Sato Y, Hatakeyama Y, Kusano T, Koyama K: Changes in tumor necrosis factor-α and interleukin-1β production following liver surgery on cirrhotic patients. Hepatogastroenterology 1996;43:1148–1153.
- Nagata S: Apoptosis by death factor. Cell 1997;88:355–365.
- Nagata S, Golstein P: The Fas death factor. Science 1995;267:1449–1456.
- Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M, Hase A, Seto Y, Nagata S: The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 1991;66:233–243.
- Cheng J, Zhou T, Liu C, Shapiro JP, Brauer MJ, Kiefer MC, Barr PJ, Mountz JD: Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science 1994;263:1759–1762.
- Tsutsui H, Kayagaki N, Kuida K, Nakano H, Hayashi N, Takeda K, Matsui K, Kashiwamura S, Hada T, Akira S, Yagita H, Okamura H, Nakanishi K: Caspase-1-independent, Fas/Fas ligand-mediated IL-18 secretion from macrophages causes acute liver injury in mice. Immunity 1999;11:359–367.
- Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H: Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol 2001;19:423–474.
- Hoshino T, Wiltrout RH, Young HA: IL-18 is a potent coinducer of IL-13 in NK and T cells: A new potential role for IL-18 in modulating the immune response. J Immunol 1999;162:5070–5077.
- Takehara T, Hayashi N, Mita E, Kanto T, Tatsumi T, Sasaki Y, Kasahara A, Hori M: Delayed Fas-mediated hepatocyte apoptosis during liver regeneration in mice: Hepatoprotective role of TNF-α. Hepatology 1998;27:1643–1651.
- Yamada Y, Kirillova I, Peschon JJ, Fausto N: Initiation of liver growth by tumor necrosis factor: Deficient liver regeneration in mice lacking type I tumor necrosis factor receptor. Proc Natl Acad Sci USA 1997;94:1441–1446.
Endo S, Yamada Y, Inada K, Nakae H: Interleukin-18 levels in patients with infectious burns; in Endo S (ed): BURN – Mediators and Pathophysiology. Tokyo, Influx Press, 2001, pp 55–59.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.