Skip to main content
SpringerLink
Log in

Cytokines in Liver Health and Disease

  • Chapter
Liver Immunology

Abstract

Cytokines are soluble peptides secreted by several kinds of cells, they mediate many immune and inflammatory reactions, and regulate several biochemical processes in and around the cells that produce them. They may act on different cell types (pleiotropic effects) and have overlapping effects (redundancy); furthermore, their action may be local or systemic. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. However, as physiologic and pathologic stimuli activate cells, the production of these molecules increases, and they orchestrate the tissue’s response to the stimulus. Phenotype of the immune response is a function of the repertoire of cytokines produced in the early phases (1).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 199.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Borish LC, Steinke JW. 2. Cytokines and chemokines. J Allergy Clin Immunol 2003; 111 (2 Suppl):S460–S475.

    Article  PubMed  CAS  Google Scholar 

  2. Bioulac-Sage P, Kuiper J, VanBerkel TJ, Balabaud C. Lymphocyte and macrophage populations in the liver. Hepatogastroenterology 1996; 43:4–14.

    PubMed  CAS  Google Scholar 

  3. Sheth K, Bankey P. The liver as an immune organ. Curr Opin Crit Care 2001; 7:99–104.

    Article  PubMed  CAS  Google Scholar 

  4. Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 1996; 17:138–146.

    Article  PubMed  CAS  Google Scholar 

  5. Hoyne GF, Lamb JR. Peptide-mediated regulation of the allergic immune response. Immunol Cell Biol 1996; 74:180–186.

    Article  PubMed  CAS  Google Scholar 

  6. Seder RA, Marth T, Sieve MC, et al. Factors involved in the differ-4 entiation of TGF-beta-producing cells from naive CD4+ T cells: IL-4 and IFN-gamma have opposing effects, while TGF-beta positively regulates its own production. J Immunol 1998; 160:5719–5728.

    PubMed  CAS  Google Scholar 

  7. Liblau RS, Singer SM, McDevitt HO. Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol Today 1995; 16:34–38.

    Article  PubMed  CAS  Google Scholar 

  8. Borchers MT, Wesselkamper S, Wert SE, Shapiro SD, Leikauf GD. Monocyte inflammation augments acrolein-induced Muc5ac expres-4 sion in mouse lung. Am J Physiol 1999; 277:L489–L497.

    PubMed  CAS  Google Scholar 

  9. Roncarolo MG, Gregori S, Levings M. Type 1 T regulatory cells and their relationship with CD4+CD25+ T regulatory cells. Novartis Found Symp 2003; 252:115–127; discussion 27–31, 203–210.

    PubMed  CAS  Google Scholar 

  10. Kunkel SL. Through the looking glass: the diverse in vivo activities of chemokines. J Clin Invest 1999; 104:1333–1334.

    PubMed  CAS  Google Scholar 

  11. Rollins BJ. Chemokines. Blood 1997; 90:909–928.

    PubMed  CAS  Google Scholar 

  12. Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity 2000; 12:121–127.

    Article  PubMed  CAS  Google Scholar 

  13. Bone-Larson CL, Simpson KJ, Colletti LM, et al. The role of chemokines in the immunopathology of the liver. Immunol Rev 2000; 177:8–20.

    Article  PubMed  CAS  Google Scholar 

  14. Bonecchi R, Bianchi G, Bordignon PP, et al. Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med 1998; 187:129–134.

    Article  PubMed  CAS  Google Scholar 

  15. Locati M, Bonecchi R, Corsi MM. Chemokines and their receptors: roles in specific clinical conditions and measurement in the clinical laboratory. Am J Clin Pathol 2005; 123 (Suppl):S82–S95.

    PubMed  CAS  Google Scholar 

  16. Shirasugi N, Wakabayashi G, Shimazu M, et al. Up-regulation of oxygen-derived free radicals by interleukin-1 in hepatic ischemia/ reperfusion injury. Transplantation 1997; 64:1398–1403.

    Article  PubMed  CAS  Google Scholar 

  17. Schutyser E, Struyf S, VanDamme J. The CC chemokine CCL20 and its receptor CCR6. Cytokine Growth Factor Rev 2003; 14: 409–426.

    Article  PubMed  CAS  Google Scholar 

  18. Moshage H. Cytokines and the hepatic acute phase response. J Pathol 1997; 181:257–266.

    Article  PubMed  CAS  Google Scholar 

  19. Baumann H, Gauldie J. The acute phase response. Immunol Today 1994; 15:74–80.

    Article  PubMed  CAS  Google Scholar 

  20. Kolesnick R, Golde DW. The sphingomyelin pathway in tumor necrosis factor and interleukin-1 signaling. Cell1994; 77:325–328.

    Article  PubMed  CAS  Google Scholar 

  21. Ihle JN. STATs: signal transducers and activators of transcription. Cell 1996; 84:331–334.

    Article  PubMed  CAS  Google Scholar 

  22. Dinarello CA, Thompson RC. Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro. Immunol Today 1991; 12:404–410.

    Article  PubMed  CAS  Google Scholar 

  23. Canbay A, Friedman S, Gores GJ. Apoptosis: the nexus of liver injury and fibrosis. Hepatology 2004; 39:273–278.

    Article  PubMed  Google Scholar 

  24. Tilg H, Diehl AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med 2000; 343:1467–1476.

    Article  PubMed  CAS  Google Scholar 

  25. Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 2001; 104: 487–501.

    Article  PubMed  CAS  Google Scholar 

  26. Canbay A, Feldstein AE, Higuchi H, et al. Kupffer cell engulfment of apoptotic bodies stimulates death ligand and cytokine expression. Hepatology 2003; 38:1188–1198.

    Article  PubMed  CAS  Google Scholar 

  27. Rust C, Gores GJ. Apoptosis and liver disease. Am J Med 2000; 108:567–574.

    Article  PubMed  CAS  Google Scholar 

  28. Reddy SA, Chaturvedi MM, Darnay BG, Chan H, Higuchi M, Aggarwal BB. Reconstitution of nuclear factor kappa B activation induced by tumor necrosis factor requires membrane-associated components. Comparison with pathway activated by ceramide. J Biol Chem 1994; 269:25,369–25,372.

    PubMed  CAS  Google Scholar 

  29. Bissell DM, Roulot D, George J. Transforming growth factor beta and the liver. Hepatology 2001; 34:859–867.

    Article  PubMed  CAS  Google Scholar 

  30. Friedman SL. Cytokines and fibrogenesis. Semin Liver Dis 1999; 19:129–140.

    PubMed  CAS  Google Scholar 

  31. Eng FJ, Friedman SL, Fibrogenesis I. New insights into hepatic stel-4 late cell activation: the simple becomes complex. Am J Physiol Gastrointest Liver Physiol 2000; 279:G7–G11.

    PubMed  CAS  Google Scholar 

  32. Pinzani M, Marra F Cytokine receptors and signaling in hepatic stellate cells. Semin Liver Dis 2001; 21:397–416.

    Article  PubMed  CAS  Google Scholar 

  33. Fausto N, Campbell JS, Riehle KJ. Liver regeneration. Hepatology 2006; 43 (2 Suppl 1):S45–S53.

    Article  PubMed  CAS  Google Scholar 

  34. Bode C, Bode JC. Activation of the innate immune system and alco-4 holic liver disease: effects of ethanol per se or enhanced intestinal translocation of bacterial toxins induced by ethanol? Alcohol Clin Exp Res 2005; 29(11 Suppl): 166S–171S.

    Article  PubMed  CAS  Google Scholar 

  35. Neuman MG. Cytokines-central factors in alcoholic liver disease. Alcohol Res Health 2003; 27:307–316.

    PubMed  Google Scholar 

  36. Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005; 115: 209–218.

    Article  PubMed  CAS  Google Scholar 

  37. Afford SC, Fisher NC, Neil DA, et al. Distinct patterns of chemokine expression are associated with leukocyte recruitment in alcoholic hepatitis and alcoholic cirrhosis. J Pathol 1998; 186: 82–89.

    Article  PubMed  CAS  Google Scholar 

  38. Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem 2000; 275: 2247–2250.

    Article  PubMed  CAS  Google Scholar 

  39. Prosser CC, Yen RD, Wu J. Molecular therapy for hepatic injury and fibrosis: where are we? World J Gastroenterol 2006; 12: 509–515.

    PubMed  CAS  Google Scholar 

  40. Benyon RC, Arthur MJ. Extracellular matrix degradation and the role of hepatic stellate cells. Semin Liver Dis 2001; 21:373–384.

    Article  PubMed  CAS  Google Scholar 

  41. Holmbeck K, Bianco P, Caterina J, et al. MT 1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue dis-4 ease due to inadequate collagen turnover. Cell 1999; 99:81–92.

    Article  PubMed  CAS  Google Scholar 

  42. Marra F, Aleffi S, Bertolani C, Petrai I, Vizzutti F. Review article: the pathogenesis of fibrosis in non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2005; 22(Suppl 2):44–47.

    Article  PubMed  Google Scholar 

  43. Valenti L, Fracanzani AL, Dongiovanni P, et al. Tumor necrosis fac-4 tor alpha promoter polymorphisms and insulin resistance in nonal-4 coholic fatty liver disease. Gastroenterology 2002; 122: 274–280.

    Article  PubMed  CAS  Google Scholar 

  44. Bugianesi E, Zannoni C, Vanni E, Marzocchi R, Marchesini G. Non-4 alcoholic fatty liver and insulin resistance: a cause-effect relation-4 ship? Dig Liver Dis 2004; 36:165–173.

    Article  PubMed  CAS  Google Scholar 

  45. Marra F. Leptin and liver fibrosis: a matter of fat. Gastroenterology 2002; 122:1529–1532.

    Article  PubMed  Google Scholar 

  46. Cao Q, Mak KM, Ren C, Lieber CS. Leptin stimulates tissue inhibitor of metalloproteinase-1 in human hepatic stellate cells: respective roles of the JAK/STAT and JAK-mediated H2O2-dependant MAPK pathways. J Biol Chem 2004; 279:4292–4304.

    Article  PubMed  CAS  Google Scholar 

  47. Ikejima K, Takei Y, Honda H, et al. Leptin receptor-mediated sig-4 naling regulates hepatic fibrogenesis and remodeling of extracellu-4 lar matrix in the rat. Gastroenterology 2002; 122:1399–1410.

    Article  PubMed  CAS  Google Scholar 

  48. Bertoletti A, Ferrari C. Kinetics of the immune response during HBV and HCV infection. Hepatology 2003; 38:4–13.

    Article  PubMed  CAS  Google Scholar 

  49. Tseng CT, Miskovsky E, Houghton M, Klimpel GR Characterization of liver T-cell receptor gammadelta T cells obtained from individu-4 als chronically infected with hepatitis C virus (HCV): evidence for these T cells playing a role in the liver pathology associated with HCV infections. Hepatology 2001; 33:1312–1320.

    Article  PubMed  CAS  Google Scholar 

  50. Foster GR. Interferons in host defense. Semin Liver Dis 1997; 17:287–295.

    Article  PubMed  CAS  Google Scholar 

  51. Rosen HR. Hepatitis C pathogenesis: mechanisms of viral clearance and liver injury. Liver Transplant 2003; 9:S35–S43.

    Article  Google Scholar 

  52. Menne S, Roneker CA, Roggendorf M, Gerin JL, Cote PJ, Tennant BC. Deficiencies in the acute-phase cell-mediated immune response to viral antigens are associated with development of chronic woodchuck hepatitis virus infection following neonatal inoculation. J Virol 2002; 76:1769–1780.

    Article  PubMed  CAS  Google Scholar 

  53. Sprengers D, Janssen HL. Immunomodulatory therapy for chronic hepatitis B virus infection. Fundam Clin Pharmacol 2005; 19: 17–26.

    Article  PubMed  CAS  Google Scholar 

  54. Kakimi K, Lane TE, Chisari FV, Guidotti LG. Cutting edge: inhibi-4 tion of hepatitis B virus replication by activated NK T cells does not require inflammatory cell recruitment to the liver. J Immunol 2001; 167:6701–6705.

    PubMed  CAS  Google Scholar 

  55. Heise T, Guidotti LG, Cavanaugh VJ, Chisari FV. Hepatitis B virus RNA-binding proteins associated with cytokine-induced clearance of viral RNA from the liver of transgenic mice. J Virol 1999; 73:474–481.

    PubMed  CAS  Google Scholar 

  56. Koziel MJ. Cytokines in viral hepatitis. Semin Liver Dis 1999; 19:157–169.

    PubMed  CAS  Google Scholar 

  57. Thimme R, Bukh J, Spangenberg HC, et al. Viral and immunological determinants of hepatitis C virus clearance, persistence, and dis-4 ease. Proc Natl Acad Sci USA 2002; 99:15,661–15,668.

    Article  PubMed  CAS  Google Scholar 

  58. Kuzushita N, Hayashi N, Katayama K, et al. High levels of serum interleukin-10 are associated with a poor response to interferon treatment in patients with chronic hepatitis C. Scand J Gastroenterol 1997; 32:169–174.

    Article  PubMed  CAS  Google Scholar 

  59. Llorent L, Richaud-Patin Y, Alcocer-Castillejos N, et al. Cytokine gene expression in cirrhotic and non-cirrhotic human liver. J Hepatol 1996; 24:555–563.

    Article  PubMed  CAS  Google Scholar 

  60. Crotta S, Stilla A, Wack A, et al. Inhibition of natural killer cells through engagement of CD81 by the major hepatitis C virus enve-4 lope protein. J Exp Med 2002; 195:35–41.

    Article  PubMed  CAS  Google Scholar 

  61. Apolinario A, Majano PL, Alvarez-Perez E, et al. Increased expres-4 sion of T cell chemokines and their receptors in chronic hepatitis C: relationship with the histological activity of liver disease. Am J Gastroenterol 2002; 97:2861–2870.

    Article  PubMed  CAS  Google Scholar 

  62. Selmaj K, Raine CS, Farooq M, Norton WT, Brosnan CF. Cytokine cytotoxicity against oligodendrocytes. Apoptosis induced by lymphotoxin. J Immunol 1991; 147:1522–1529.

    PubMed  CAS  Google Scholar 

  63. Foulis AK, McGill M, Farquharson MA. Insulitis in type 1 (insulin-dependent) diabetes mellitus in man—macrophages, lym-4 phocytes, and interferon-gamma containing cells. J Pathol 1991; 165:97–103.

    Article  PubMed  CAS  Google Scholar 

  64. Matthews N, Emery P, Pilling D, Akbar A, Salmon M. Subpopulations of primed T helper cells in rheumatoid arthritis. Arthritis Rheum 1993; 36:603–607.

    Article  PubMed  CAS  Google Scholar 

  65. Harada K, Van deWater J, Leung PS, et al. In situ nucleic acid hybridization of cytokines in primary biliary cirrhosis: predomi-4 nance of the Th1 subset. Hepatology 1997; 25:791–796.

    Article  PubMed  CAS  Google Scholar 

  66. Martinez OM, Villanueva JC, Gershwin ME, Krams SM. Cytokine patterns and cytotoxic mediators in primary biliary cirrhosis. Hepatology 1995; 21:113–119.

    PubMed  CAS  Google Scholar 

  67. Shindo M, Mullin GE, Braun-Elwert L, Bergasa NV, Jones EA, James SP Cytokine mRNA expression in the liver of patients with primary biliary cirrhosis (PBC) and chronic hepatitis B (CHB). Clin Exp Immunol 1996; 105:254–259.

    Article  PubMed  CAS  Google Scholar 

  68. Nagano T, Yamamoto K, Matsumoto S, et al. Cytokine profile in the liver of primary biliary cirrhosis. J Clin Immunol 1999; 19:422–427.

    Article  PubMed  CAS  Google Scholar 

  69. Tjandra K, Sharkey KA, Swain MG. Progressive development of a Th1-type hepatic cytokine profile in rats with experimental cholangitis. Hepatology 2000; 31:280–290.

    Article  PubMed  CAS  Google Scholar 

  70. Bo X, Broome U, Remberger M, Sumitran-Holgersson S. Tumour necrosis factor alpha impairs function of liver derived T lympho-4 cytes and natural killer cells in patients with primary sclerosing cholangitis. Gut 2001; 49:131–141.

    Article  PubMed  CAS  Google Scholar 

  71. Spengler U, Moller A, Jung MC, et al. T lymphocytes from patients with primary biliary cirrhosis produce reduced amounts of lymphotoxin, tumor necrosis factor and interferon-gamma upon mitogen stimulation. J Hepatol 1992; 15:129–135.

    Article  PubMed  CAS  Google Scholar 

  72. Spirli C, Fabris L, Duner E, et al. Cytokine-stimulated nitric oxide production inhibits adenylyl cyclase and cAMP-dependent secretion in cholangiocytes. Gastroenterology 2003; 124:737–753.

    Article  PubMed  CAS  Google Scholar 

  73. Vergani D, Choudhuri K, Bogdanos DP, Mieli-Vergani G. Pathogenesis of autoimmune hepatitis. Clin Liver Dis 2002; 6:727–737.

    Article  PubMed  Google Scholar 

  74. Tanaka Y, Takahashi A, Watanabe K, et al. A pivotal role of IL-12 in Th1-dependent mouse liver injury. Int Immunol 1996; 8:569–576.

    Article  PubMed  CAS  Google Scholar 

  75. Nicoletti F, Di Marco R, Zaccone P, et al. Murine concanavalin A-induced hepatitis is prevented by interleukin 12 (IL-12) antibody and exacerbated by exogenous IL-12 through an interferon-gammadependent mechanism. Hepatology 2000; 32:728–733.

    Article  PubMed  CAS  Google Scholar 

  76. Trinchieri G, Pflanz S, Kastelein RA. The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses. Immunity 2003; 19:641–644.

    Article  PubMed  CAS  Google Scholar 

  77. Humar A, Kosari K, Sielaff TD, et al. Liver regeneration after adult living donor and deceased donor split-liver transplants. Liver Transplant 2004; 10:374–378.

    Article  Google Scholar 

  78. Iwai M, Cui TX, Kitamura H, Saito M, Shimazu T. Increased secretion of tumour necrosis factor and interleukin 6 from isolated, perfused liver of rats after partial hepatectomy. Cytokine 2001; 13:60–64.

    Article  PubMed  CAS  Google Scholar 

  79. Serandour AL, Loyer P, Gamier D, et al. TNFalpha-mediated extra-4 cellular matrix remodeling is required for multiple division cycles in rat hepatocytes. Hepatology 2005; 41:478–486.

    Article  PubMed  CAS  Google Scholar 

  80. Blindenbacher A, Wang X, Langer I, Savino R, Terracciano L, Heim MH. Interleukin 6 is important for survival after partial hepatec-4 tomy in mice. Hepatology 2003; 38:674–682.

    Article  PubMed  CAS  Google Scholar 

  81. Lentsch AB, Kato A, Yoshidome H, McMasters KM, Edwards MJ. Inflammatory mechanisms and therapeutic strategies for warm hepatic ischemia/reperfusion injury. Hepatology 2000; 32: 169–173.

    Article  PubMed  CAS  Google Scholar 

  82. Boros P, Bromberg JS. New cellular and molecular immune pathways in ischemia/reperfusion injury. Am J Transplant 2006; 6:652–658.

    Article  PubMed  CAS  Google Scholar 

  83. Colletti LM, Kunkel SL, Walz A, et al. Chemokine expression during hepatic ischemia/reperfusion-induced lung injury in the rat. The role of epithelial neutrophil activating protein. J Clin Invest 1995; 95:134–141.

    PubMed  CAS  Google Scholar 

  84. Lentsch AB, Yoshidome H, Kato A, et al. Requirement for interleukin-12 in the pathogenesis of warm hepatic ischemia/reperfusion injury in mice. Hepatology 1999; 30:1448–1453.

    Article  PubMed  CAS  Google Scholar 

  85. Yoshidome H, Kato A, Edwards MJ, Lentsch AB. Interleukin-10 suppresses hepatic ischemia/reperfusion injury in mice: implications of a central role for nuclear factor kappaB. Hepatology 1999; 30: 203–208.

    Article  PubMed  CAS  Google Scholar 

  86. Huang YS, Chan CY, Wu JC, Pai CH, Chao Y, Lee SD. Serum lev-4 els of interleukin-8 in alcoholic liver disease: relationship with disease stage, biochemical parameters and survival. J Hepatol 1996; 24:377–384.

    Article  PubMed  CAS  Google Scholar 

  87. Uguccioni M, Meliconi R, Nesci S, et al. Elevated interleukin-8 serum concentrations in beta-thalassemia and graft-versus-host dis-4 ease. Blood 1993; 81:2252–2256.

    PubMed  CAS  Google Scholar 

  88. Zhang P, Xie M, Zagorski J, Spitzer JA. Attenuation of hepatic neu-4 trophil sequestration by anti-CINC antibody in endotoxic rats. Shock 1995; 4:262–268.

    Article  PubMed  CAS  Google Scholar 

  89. Colletti LM, Green M, Burdick MD, Kunkel SL, Strieter RM. Proliferative effects of CXC chemokines in rat hepatocytes in vitro and in vivo. Shock 1998; 10:248–257.

    PubMed  CAS  Google Scholar 

  90. Mercer-Jones MA, Shrotri MS, Peyton JC, Remick DG, Cheadle WG. Neutrophil sequestration in liver and lung is differentially reg-4 ulated by C-X-C chemokines during experimental peritonitis. Inflammation 1999; 23:305–319.

    PubMed  CAS  Google Scholar 

  91. Lentsch AB, Yoshidome H, Cheadle WG, Miller FN, Edwards MJ. Chemokine involvement in hepatic ischemia/reperfusion injury in mice: roles for macrophage inflammatory protein-2 and KC. Hepatology 1998; 27:1172–1177.

    Article  PubMed  CAS  Google Scholar 

  92. Tilg H, Ceska M, Vogel W, Herold M, Margreiter R, Huber C. Interleukin-8 serum concentrations after liver transplantation. Transplantation 1992; 53:800–803.

    PubMed  CAS  Google Scholar 

  93. Nanji AA, Jokelainen K, Rahemtulla A, et al. Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat. Hepatology 1999; 30:934–943.

    Article  PubMed  CAS  Google Scholar 

  94. Shields PL, Morland CM, Salmon M, Qin S, Hubscher SG, Adams DH. Chemokine and chemokine receptor interactions provide a mechanism for selective T cell recruitment to specific liver com-4 partments within hepatitis C-infected liver. J Immunol 1999; 163:6236–6243.

    PubMed  CAS  Google Scholar 

  95. Yoong KF, Afford SC, Jones R, et al. Expression and function of CXC and CC chemokines in human malignant liver tumors: a role for human monokine induced by gamma-interferon in lymphocyte recruitment to hepatocellular carcinoma. Hepatology 1999; 30: 100–111.

    Article  PubMed  CAS  Google Scholar 

  96. Goddard S, Williams A, Morland C, et al. Differential expression of chemokines and chemokine receptors shapes the inflammatory response in rejecting human liver transplants. Transplantation 2001; 72:1957–1967.

    Article  PubMed  CAS  Google Scholar 

  97. Shibuta K, Begum NA, Mori M, Shimoda K, Akiyoshi T, Barnard GF. Reduced expression of the CXC chemokine hIRH/SDF-1alpha mRNA in hepatoma and digestive tract cancer. Int J Cancer 1997; 73:656–662.

    Article  PubMed  CAS  Google Scholar 

  98. Narumi S, Tominaga Y, Tamaru M, et al. Expression of IFN-inducible protein-10 in chronic hepatitis. J Immunol 1997; 158:5536–5544.

    PubMed  CAS  Google Scholar 

  99. Marra F, DeFranco R, Grappone C, et al. Increased expression of monocyte chemotactic protein-1 during active hepatic fibrogenesis: correlation with monocyte infiltration. Am J Pathol 1998; 152: 423–430.

    PubMed  CAS  Google Scholar 

  100. Salkowski CA, Detore G, Franks A, Falk MC, Vogel SN. Pulmonary and hepatic gene expression following cecal ligation and puncture: monophosphoryl lipid A prophylaxis attenuates sepsis-induced cytokine and chemokine expression and neutrophil infiltration. Infect Immun 1998; 66:3569–3578.

    PubMed  CAS  Google Scholar 

  101. Murai M, Yoneyama H, Harada A, et al. Active participation of CCR5(+)CD8(+) T lymphocytes in the pathogenesis of liver injury in graft-versus-host disease. J Clin Invest 1999; 104: 49–57.

    PubMed  CAS  Google Scholar 

  102. Adams DH, Hubscher S, Fear J, Johnston J, Shaw S, Afford S. Hepatic expression of macrophage inflammatory protein-1 alpha and macrophage inflammatory protein-1 beta after liver transplanta-4 tion. Transplantation 1996; 61:817–825.

    Article  PubMed  CAS  Google Scholar 

  103. Salazar-Mather TP, Orange JS, Biron CA. Early murine cytomegalovirus (MCMV) infection induces liver natural killer (NK) cell inflammation and protection through macrophage inflam-4 matory protein 1alpha (MIP-1alpha)-dependent pathways. J Exp Med 1998; 187:1–14.

    Article  PubMed  CAS  Google Scholar 

  104. Fisher NC, Neil DA, Williams A, Adams DH. Serum concentrations and peripheral secretion of the beta chemokines monocyte chemoattractant protein 1 and macrophage inflammatory protein 1alpha in alcoholic liver disease. Gut 1999; 45:416–420.

    Article  PubMed  CAS  Google Scholar 

  105. Hirano F, Kobayashi A, Hirano Y, Nomura Y, Fukawa E, Makino I. Bile acids regulate RANTES gene expression through its cognate NF-kappaB binding sites. Biochem Biophys Res Commun 2001; 288:1095–1101.

    Article  PubMed  CAS  Google Scholar 

  106. Kusano F, Tanaka Y, Marumo F, Sato C. Expression of C-C chemokines is associated with portal and periportal inflammation in the liver of patients with chronic hepatitis C. Lab Invest 2000; 80:415–422.

    PubMed  CAS  Google Scholar 

  107. Muruve DA, Barnes MJ, Stillman IE, Libermann TA. Adenoviral gene therapy leads to rapid induction of multiple chemokines and acute neutrophil-dependent hepatic injury in vivo. Hum Gene Ther 1999; 10:965–976.

    Article  PubMed  CAS  Google Scholar 

  108. Nagral A, Ben-Ari Z, Dhillon AP, Burroughs AK Eosinophils in acute cellular rejection in liver allografts. Liver Transplant Surg 1998; 4:355–362.

    Article  CAS  Google Scholar 

  109. Pham BN, Bemuau J, Durand F, et al. Eotaxin expression and eosinophil infiltrate in the liver of patients with drug-induced liver disease. J Hepatol 2001; 34:537–547.

    Article  PubMed  CAS  Google Scholar 

  110. Yoneyama H, Harada A, Imai T, et al. Pivotal role of TARC, a CC chemokine, in bacteria-induced fulminant hepatic failure in mice. J Clin Invest 1998; 102:1933–1941.

    Article  PubMed  CAS  Google Scholar 

  111. Chvatchko Y, Hoogewerf AJ, Meyer A, et al. A key role for CC chemokine receptor 4 in lipopolysaccharide-induced endotoxic shock. J Exp Med 2000; 191:1755–1764.

    Article  PubMed  CAS  Google Scholar 

  112. Matsukawa A, Kaplan MH, Hogaboam CM, Lukacs NW, Kunkel SL. Pivotal role of signal transducer and activator of transcription (Stat)4 and Stat6 in the innate immune response during sepsis. J Exp Med 2001; 193:679–688.

    Article  PubMed  CAS  Google Scholar 

  113. Shimizu Y, Murata H, Kashii Y, et al. CC-chemokine receptor 6 and its ligand macrophage inflammatory protein 3alpha might be involved in the amplification of local necroinflammatory response in the liver. Hepatology 2001; 34:311–319.

    Article  PubMed  CAS  Google Scholar 

  114. Simpson KJ, Henderson NC, Bone-Larson CL, Lukacs NW, Hogaboam CM, Kunkel SL. Chemokines in the pathogenesis of liver disease: so many players with poorly defined roles. Clin Sci (Lond) 2003; 104:47–63.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Internal Medicine, Department of Medicine, Surgery and Dentistry, San Paolo School of Medicine, University of Milan, Milan, Italy

    Pietro Invernizzi MD, PhD

  2. Division of Internal Medicine, San Paolo School of Medicine, University of Milan, Milan, Italy

    Ilaria Bianchi MD & Raffaella Bonecchi PhD

  3. Institute of General Pathology, Faculty of Medicine, University of Milan, Milan, Italy

    Massimo Locati MD

  4. Istituto Clinico Humanitas, Rozzano, Italy

    Massimo Locati MD

  5. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA

    Raffaella Bonecchi PhD

Authors
  1. Pietro Invernizzi MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ilaria Bianchi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Massimo Locati MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Raffaella Bonecchi PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carlo Selmi MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA

    M. Eric Gershwin MD, FACP

  2. Departments of Medicine and Surgery Baylor Liver Health, Baylor College of Medicine, Houston, TX

    John M. Vierling MD, FACP

  3. Department of Gastroenterology, Hepatology, and Endocrinology, Medical School of Hannover, Hannover, Germany

    Michael P. Manns MD

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Invernizzi, P., Bianchi, I., Locati, M., Bonecchi, R., Selmi, C. (2007). Cytokines in Liver Health and Disease. In: Gershwin, M.E., Vierling, J.M., Manns, M.P. (eds) Liver Immunology. Humana Press. https://doi.org/10.1007/978-1-59745-518-3_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-518-3_8

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-818-8

  • Online ISBN: 978-1-59745-518-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation