Alcohol
Volume 34, Issue 1 , Pages 59-65 , August 2004

Therapeutic potential of interleukin-6 in preventing obesity- and alcohol-associated fatty liver transplant failure

  • Bin Gao

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +1-301-443-3998; fax: +1-301-480-0257.

Received 30 March 2004 ,Revised 16 July 2004 ,Accepted 20 July 2004.

References 

  1. Amersi F, Buelow R, Kato H, Ke B, Coito AJ, Shen X-D, et al. Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury. J Clin Invest. 1999;104:1631–1639
  2. Amersi F, Shen X-D, Moore C, Melinek J, Busuttil RW, Kupiec-Weglinski JW, et al. Fibronectin-α4β1 integrin-mediated blockade protects genetically fat Zucker rat livers from ischemia/reperfusion injury. Am J Pathol. 2003;162:1229–1239
  3. Busuttil RW, Tanaka K. The utility of marginal donors in liver transplantation. Liver Transpl. 2003;9:651–663
  4. Camargo CA, Madden JF, Gao W, Selvan RS, Clavien PA. Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent. Hepatology. 1997;26:1513–1520
  5. Carini R, Albano E. Recent insights on the mechanisms of liver preconditioning. Gastroenterology. 2003;125:1480–1491
  6. Chen J, Bao H, Sawyer S, Kunos G, Gao B. Effects of short and long term ethanol on the activation of signal transducer and activator transcription factor 3 in normal and regenerating liver. Biochem Biophys Res Commun. 1997;239:666–669
  7. Chen J, Clemens DL, Cederbaum AI, Gao B. Ethanol inhibits the JAK-STAT signaling pathway in freshly isolated rat hepatocytes but not in cultured hepatocytes or HepG2 cells: evidence for a lack of involvement of ethanol metabolism. Clin Biochem. 2001;34:203–209
  8. Chen J, Kunos G, Gao B. Ethanol rapidly inhibits IL-6-activated STAT3 and C/EBP mRNA expression in freshly isolated rat hepatocytes. FEBS Lett. 1999;457:162–168
  9. Chen R-H, Chang M-C, Su Y-H, Tsai Y-T, Kuo M-L. Interleukin-6 inhibits transforming growth factor-β-induced apoptosis through the phosphatidylinositol 3-kinase/Akt and signal transducers and activators of transcription 3 pathways. J Biol Chem. 1999;274:23013–23019
  10. Cressman DE, Greenbaum LE, DeAngelis RA, Ciliberto G, Furth EE, Poli V, et al. Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science. 1996;274:1379–1383
  11. Cursio R, Gugenheim J, Ricci JE, Crenesse D, Rostagno P, Maulon L, et al. A caspase inhibitor fully protects rats against lethal normothermic liver ischemia by inhibition of liver apoptosis. FASEB J. 1999;13:253–261
  12. El-Assal O, Hong F, Kim W, Radaeva S, Gao B. IL-6-deficient mice are susceptible to ethanol-induced hepatic steatosis: IL-6 protects against ethanol-induced oxidative stress and mitochondrial permeability transition in the liver. Cell Mol Immunol. 2004;1:205–211
  13. Gao W, Bentley RC, Madden JF, Clavien P-A. Apoptosis of sinusoidal endothelial cells is a critical mechanism of preservation injury in rat liver transplantation. Hepatology. 1998;27:1652–1660
  14. García Ureña MA, Colina Ruiz-Delgado F, Moreno González E, Jiménez Romero C, García García I, Loinzaz Segurola C, et al. Hepatic steatosis in liver transplant donors: common feature of donor population?. World J Surg. 1998;22:837–844
  15. Haga S, Terui K, Zhang HQ, Enosawa S, Ogawa W, Inoue H, et al. Stat3 protects against Fas-induced liver injury by redox-dependent and -independent mechanisms. J Clin Invest. 2003;112:989–998
  16. Hertl M, Hertl MC, Malagó M, Broelsch CE. In vivo protection of the pig liver against ischemia/reperfusion injury by tauroursodeoxycholate. Langenbecks Arch Surg. 1999;384:461–466
  17. Hong F, Jaruga B, Kim WH, Radaeva S, El-Assal ON, Tian Z, et al. Opposing roles of STAT1 and STAT3 in T cell–mediated hepatitis: regulation by SOCS. J Clin Invest. 2002;110:1503–1513
  18. Hong F, Kim W-H, Tian Z, Jaruga B, Ishac E, Shen X, et al. Elevated interleukin-6 during ethanol consumption acts as a potential endogenous protective cytokine against ethanol-induced apoptosis in the liver: involvement of induction of Bcl-2 and Bcl-xL proteins. Oncogene. 2002;21:32–43
  19. Jaeschke H. Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning. Am J Physiol Gastrointest Liver Physiol. 2003;284:G15–G26
  20. Kato Y, Shimazu M, Kondo M, Uchida K, Kumamoto Y, Wakabayashi G, et al. Bilirubin rinse: a simple protectant against the rat liver graft injury mimicking heme oxygenase-1 preconditioning. Hepatology. 2003;38:364–373
  21. Kohli V, Selzner M, Madden JF, Bentley RC, Clavien P-A. Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver. Transplantation. 1999;67:1099–1105
  22. Kovalovich K, DeAngelis RA, Li W, Furth EE, Ciliberto G, Taub R. Increased toxin-induced liver injury and fibrosis in interleukin-6-deficient mice. Hepatology. 2000;31:149–159
  23. Kovalovich K, Li W, DeAngelis R, Greenbaum LE, Ciliberto G, Taub R. Interleukin-6 protects against Fas-mediated death by establishing a critical level of anti-apoptotic hepatic proteins FLIP, Bcl-2, and Bcl- xL. J Biol Chem. 2001;276:26605–26613
  24. Lehmann TG, Wheeler MD, Froh M, Schwabe RF, Bunzendahl H, Samulski RJ, et al. Effects of three superoxide dismutase genes delivered with an adenovirus on graft function after transplantation of fatty livers in the rat. Transplantation. 2003;76:28–37
  25. Lehmann TG, Wheeler MD, Schwabe RF, Connor HD, Schoonhoven R, Bunzendahl H, et al. Gene delivery of Cu/Zn-superoxide dismutase improves graft function after transplantation of fatty livers in the rat. Hepatology. 2000;32:1255–1264
  26. Lemasters JJ, Thurman RG. Reperfusion injury after liver preservation for transplantation. Annu Rev Pharmacol Toxicol. 1997;37:327–338
  27. Li W, Liang X, Kellendonk C, Poli V, Taub R. STAT3 contributes to the mitogenic response of hepatocytes during liver regeneration. J Biol Chem. 2002;277:28411–28417
  28. Marsman WA, Wiesner RH, Rodriguez L, Batts KP, Porayko MK, Hay JE, et al. Use of fatty donor liver is associated with diminished early patient and graft survival. Transplantation. 1996;62:1246–1251
  29. Masubuchi Y, Bourdi M, Reilly TP, Graf MLM, George JW, Pohl LR. Role of interleukin-6 in hepatic heat shock protein expression and protection against acetaminophen-induced liver disease. Biochem Biophys Res Commun. 2003;304:207–212
  30. Mizuhara H, Uno M, Seki N, Yamashita M, Yamaoka M, Ogawa T, et al. Critical involvement of interferon γ in the pathogenesis of T-cell activation-associated hepatitis and regulatory mechanisms of interleukin-6 for the manifestations of hepatitis. Hepatology. 1996;23:1608–1615
  31. Rao ARN, Chui AKK, Shi LW, Tsai L, Leon CD, Sheil AGR. Is donor obesity related to liver steatosis and liver graft dysfunction in liver transplantation?. Transplant Proc. 2000;32:2103
  32. Rinella ME, Alonso E, Rao S, Whitington P, Fryer J, Abecassis M, et al. Body mass index as a predictor of hepatic steatosis in living liver donors. Liver Transpl. 2001;7:409–414
  33. Seifalian AM, Chidambaram V, Rolles K, Davidson BR. In vivo demonstration of impaired microcirculation in steatotic human liver grafts. Liver Transpl Surg. 1998;4:71–77
  34. Seifalian AM, Piasecki C, Agarwal A, Davidson BR. The effect of graded steatosis on flow in the hepatic parenchymal microcirculation. Transplantation. 1999;68:780–784
  35. Selzner M, Camargo CA, Clavien P-A. Ischemia impairs liver regeneration after major tissue loss in rodents: protective effects of interleukin-6. Hepatology. 1999;30:469–475
  36. Selzner M, Clavien P-A. Fatty liver in liver transplantation and surgery. Semin Liver Dis. 2001;21:105–113
  37. Selzner M, Graf R, Clavien P-A. IL-6: a magic potion for liver transplantation?. Gastroenterology. 2003;125:256–259
  38. Selzner M, Rüdiger HA, Sindram D, Madden J, Clavien P-A. Mechanisms of ischemic injury are different in the steatotic and normal rat liver. Hepatology. 2000;32:1280–1288
  39. Selzner N, Rüdiger H, Graf R, Clavien P-A. Protective strategies against ischemic injury of the liver. Gastroenterology. 2003;125:917–936
  40. Selzner N, Selzner M, Jochum W, Clavien P-A. Ischemic preconditioning protects the steatotic mouse liver against reperfusion injury: an ATP dependent mechanism. J Hepatol. 2003;39:55–61
  41. Selzner N, Selzner M, Tian Y, Kadry Z, Clavien P-A. Cold ischemia decreases liver regeneration after partial liver transplantation in the rat: a TNF-α/IL-6-dependent mechanism. Hepatology. 2002;36:812–818
  42. Serafin A, Roselló-Catafau J, Prats N, Xaus C, Gelpí E, Peralta C. Ischemic preconditioning increases the tolerance of fatty liver to hepatic ischemia-reperfusion injury in the rat. Am J Pathol. 2002;161:587–601
  43. Streetz KL, Tacke F, Leifeld L, Wüstefeld T, Graw A, Klein C, et al. Interleukin 6/gp130-dependent pathways are protective during chronic liver diseases. Hepatology. 2003;38:218–229
  44. Streetz KL, Wüstefeld T, Klein C, Kallen K-J, Tronche F, Betz UAK, et al. Lack of gp130 expression in hepatocytes promotes liver injury. Gastroenterology. 2003;125:532–543
  45. Sun C-K, Zhang X-Y, Zimmermann A, Davis G, Wheatley AM. Effect of ischemia-reperfusion injury on the microcirculation of the steatotic liver of the Zucker rat. Transplantation. 2001;72:1625–1631
  46. Sun Z, Klein AS, Radaeva S, Hong F, El-Assal O, Pan H-N, et al. In vitro interleukin-6 treatment prevents mortality associated with fatty liver transplants in rats. Gastroenterology. 2003;125:202–215
  47. Taga T, Kishimoto T. gp130 and the interleukin-6 family of cytokines. Annu Rev Immunol. 1997;15:797–819
  48. Taub R. Hepatoprotection via the IL-6/Stat3 pathway. J Clin Invest. 2003;112:978–980
  49. Teramoto K, Bowers JL, Kruskal JB, Clouse ME. Hepatic microcirculatory changes after reperfusion in fatty and normal liver transplantation in the rat. Transplantation. 1993;56:1076–1082
  50. Todo S, Demetris AJ, Makowka L, Teperman L, Podesta L, Shaver T, et al. Primary nonfunction of hepatic allografts with preexisting fatty infiltration. Transplantation. 1989;47:903–905
  51. Wuestefeld T, Klein C, Streetz KL, Betz U, Lauber J, Buer J, et al. Interleukin-6/glycoprotein 130-dependent pathways are protective during liver regeneration. J Biol Chem. 2003;278:11281–11288
  52. Yokoyama I, Kobayashi T, Negita M, Hayashi S, Yasutomi M, Katayama A, et al. Liberation of vasoactive substances and its prevention with thromboxane A2 synthase inhibitor in pig liver transplantation. Transpl Int. 1996;9:76–81
  53. Zamboni F, Franchello A, David E, Rocca G, Ricchiuti A, Lavezzo B, et al. Effect of macrovescicular steatosis and other donor and recipient characteristics on the outcome of liver transplantation. Clin Transplant. 2001;15:53–57
  54. Zhong Z, Lemasters JJ. Role of free radicals in failure of fatty liver grafts caused by ethanol. Alcohol. 2004;34:49–58

PII: S0741-8329(04)00154-5

doi: 10.1016/j.alcohol.2004.07.006

Alcohol
Volume 34, Issue 1 , Pages 59-65 , August 2004