Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000069.xml
Download PDF
Semin Liver Dis 2004; 24(3): 273-287
DOI: 10.1055/s-2004-832940
DOI: 10.1055/s-2004-832940
Immunologic Mechanisms of Alcoholic Liver Injury
Further Information
Publication History
Publication Date:
03 September 2004 (online)
Clinically, the association of alcoholic liver disease (ALD) with circulating autoantibodies, hypergammaglobulinemia, antibodies to unique hepatic proteins, and cytotoxic lymphocytes reacting against autologous hepatocytes strongly suggests altered immune regulation with an increased activity toward normal self-proteins (loss of tolerance). Experimentally, there are several immune responses generated specifically recognizing self-proteins that are modified by metabolites of alcohol. These data strongly suggest that immune reactions may play a significant role in inducing and sustaining an inflammatory cascade of tissue damage to the liver. Additional support for this comes from the observation that the histological appearance of livers with ALD is that of a chronic active hepatitis-like inflammatory disease. Therefore, the hypothesis that immune mechanisms are involved in recurrent alcoholic hepatitis, although not summarily proven, is reasonable, supported by clinical and experimental evidence, and the subject of this article.
KEYWORDS
Antibodies - T cells - adducts - autoimmunity - immune responses
REFERENCES
- 1 Kovacs E J, Messingham K A. Influence of alcohol and gender on immune response. Alcohol Res Health. 2002; 26 257-263
- 2 Cook R T. Alcohol abuse, alcoholism, and damage to the immune system-a review. Alcohol Clin Exp Res. 1998; 22 1927-1942
- 3 Diaz L E, Montero A, Gonzalez-Gross M et al.. Influence of alcohol consumption on immunological status: a review. Eur J Clin Nutr. 2002; 56(Suppl 3) S50-S53
- 4 Nelson S, Kolls J K. Alcohol, host defence and society. Nat Rev Immunol. 2002; 2 205-209
- 5 Messingham K A, Faunce D E, Kovacs E J. Alcohol, injury, and cellular immunity. Alcohol. 2002; 28 137-149
- 6 Bailey R J, Krasner N, Eddleston A L, et a l. Histocompatibility antigens, autoantibodies, and immunoglobulins in alcoholic liver disease. BMJ. 1976; 2 727-729
- 7 Zetterman R K, Sorrell M F. Immunologic aspects of alcoholic liver disease. Gastroenterology. 1981; 81 616-624
- 8 Baddour N, Demetris A J, Shah G, Tringali R, Van Thiel D H. The prevalence, rate of onset and spectrum of histologic liver disease in alcohol abusing liver allograft recipients. Gastroenterology. 1992; 102 A777
- 9 Carithers Jr R L, Herlong H F, Diehl A M et al.. Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial. Ann Intern Med. 1989; 110 685-690
- 10 Ramond M J, Poynard T, Rueff B et al.. A randomized trial of prednisolone in patients with severe alcoholic hepatitis. N Engl J Med. 1992; 326 507-512
- 11 Seeff L B, Cuccherini B A, Zimmerman H J, Adler E, Benjamin S B. Acetaminophen hepatotoxicity in alcoholics. A therapeutic misadventure. Ann Intern Med. 1986; 104 399-404
- 12 Moshage H, Casini A, Lieber C S. Acetaldehyde selectively stimulates collagen production in cultured rat liver fat-storing cells but not in hepatocytes. Hepatology. 1990; 12 511-518
- 13 Casini A, Cunningham M, Rojkind M, Lieber C S. Acetaldehyde increases procollagen type I and fibronectin gene transcription in cultured rat fat-storing cells through a protein synthesis-dependent mechanism. Hepatology. 1991; 13 758-765
- 14 Pares A, Potter J J, Rennie L, Mezey E. Acetaldehyde activates the promoter of the mouse alpha 2(I) collagen gene. Hepatology. 1994; 19 498-503
- 15 Wands J R, Carter E A, Bucher N L, Isselbacher K J. Inhibition of hepatic regeneration in rats by acute and chronic ethanol intoxication. Gastroenterology. 1979; 77 528-531
- 16 Leevy C M. Fatty liver: a study of 270 patients with biopsy proven fatty liver and review of the literature. Medicine (Baltimore). 1962; 41 249-276
- 17 Gluud C, Christoffersen P, Eriksen J, Wantzin P, Knudsen B B. Influence of ethanol on development of hyperplastic nodules in alcoholic men with micronodular cirrhosis. Gastroenterology. 1987; 93 256-260
- 18 Worrall S, Thiele G M. Protein modification in ethanol toxicity. Adverse Drug React Toxicol Rev. 2001; 20 133-159
- 19 Klassen L W, Tuma D, Sorrell M F. Immune mechanisms of alcohol-induced liver disease. Hepatology. 1995; 22 355-357
- 20 Tuma D J, Sorrel M F. The role of acetaldehyde adducts in liver injury. In: Hall P Alcoholic Liver Disease: Pathology and Pathogenesis, 2nd ed. London; Edward Arnold 1995: 89-99
MissingFormLabel
- 21 Sorrell M F, Tuma D J. Hypothesis: alcoholic liver injury and the covalent binding of acetaldehyde. Alcohol Clin Exp Res. 1985; 9 306-309
- 22 Tuma D J, Newman M R, Donohue Jr T M, Sorrell M F. Covalent binding of acetaldehyde to proteins: participation of lysine residues. Alcohol Clin Exp Res. 1987; 11 579-584
- 23 Kamimura S, Gaal K, Britton R S et al.. Increased 4-hydroxynonenal levels in experimental alcoholic liver disease: association of lipid peroxidation with liver fibrogenesis. Hepatology. 1992; 16 448-453
- 24 Benedetti A, Comporti M. Formation reactions and toxicity of aldehydes produced in the course of lipid peroxidation in cellular membranes. Bioelectrochem Bioenerg. 1987; 18 187-202
- 25 Israel Y, Orrego H, Niemela O. Immune responses to alcohol metabolites: pathogenic and diagnostic implications. Semin Liver Dis. 1988; 8 81-90
- 26 Tuma D J, Klassen L W. Immune responses to acetaldehyde-protein adducts: role in alcoholic liver disease. Gastroenterology. 1992; 103 1969-1973
- 27 Crossley I R, Neuberger J, Davis M, Williams R, Eddleston A L. Ethanol metabolism in the generation of new antigenic determinants on liver cells. Gut. 1986; 27 186-189
- 28 Lin R C, Smith R S, Lumeng L. Detection of a protein-acetaldehyde adduct in the liver of rats fed alcohol chronically. J Clin Invest. 1988; 81 615-619
- 29 Niemela O, Parkkila S, Yla-Herttuala S et al.. Sequential acetaldehyde production, lipid peroxidation, and fibrogenesis in micropig model of alcohol-induced liver disease. Hepatology. 1995; 22 1208-1214
- 30 Hoerner M, Behrens U J, Worner T, Lieber C S. Humoral immune response to acetaldehyde adducts in alcoholic patients. Res Commun Chem Pathol Pharmacol. 1986; 54 3-12
- 31 Worrall S, de Jersey J, Shanley B C, Wilce P A. Ethanol induces the production of antibodies to acetaldehyde- modified epitopes in rats. Alcohol Alcohol. 1989; 24 217-223
- 32 Lin R C, Lumeng L, Shahidi S, Kelly T, Pound D C. Protein-acetaldehyde adducts in serum of alcoholic patients. Alcohol Clin Exp Res. 1990; 14 438-443
- 33 Niemela O, Juvonen T, Parkkila S. Immunohistochemical demonstration of acetaldehyde-modified epitopes in human liver after alcohol consumption. J Clin Invest. 1991; 87 1367-1374
- 34 Terabayashi H, Kolber M A. The generation of cytotoxic T lymphocytes against acetaldehyde-modified syngeneic cells. Alcohol Clin Exp Res. 1990; 14 893-899
- 35 Yokoyama H, Nagata S, Moriya S et al.. Hepatic fibrosis produced in guinea pigs by chronic ethanol administration and immunization with acetaldehyde adducts. Hepatology. 1995; 21 1438-1442
- 36 Worrall S, de Jersey J, Wilce P A. Liver damage in ethanol-fed rats injected with acetaldehyde modified proteins. Alcohol Clin Exp Res. 1992; 16 623
- 37 Israel Y, Hurwitz E, Niemela O, Arnon R. Monoclonal and polyclonal antibodies against acetaldehyde- containing epitopes in acetaldehyde-protein adducts. Proc Natl Acad Sci USA. 1986; 83 7923-7927
- 38 Worrall S, de Jersey J, Shanley B C, Wilce P A. Antibodies against acetaldehyde-modified epitopes: an elevated IgA response in alcoholics. Eur J Clin Invest. 1991; 21 90-95
- 39 Worrall S, de Jersey J, Shanley B C, Wilce P A. Detection of stable acetaldehyde-modified proteins in the livers of ethanol-fed rats. Alcohol Alcohol. 1991; 26 437-444
- 40 Niemela O, Parkkila S, Juvonen R O et al.. Cytochromes P450 2A6, 2E1, and 3A and production of protein-aldehyde adducts in the liver of patients with alcoholic and non-alcoholic liver diseases. J Hepatol. 2000; 33 893-901
- 41 Klassen L W, Tuma D J, Sorrell M F et al.. Detection of reduced acetaldehyde protein adducts using a unique monoclonal antibody. Alcohol Clin Exp Res. 1994; 18 164-171
- 42 Eriksson C J, Atkinson N, Petersen D R, Deitrich R A. Blood and liver acetaldehyde concentrations during ethanol oxidation in C57 and DBA mice. Biochem Pharmacol. 1984; 33 2213-2216
- 43 Houglum K, Filip M, Witztum J L, Chojkier M. Malondialdehyde and 4-hydroxynonenal protein adducts in plasma and liver of rats with iron overload. J Clin Invest. 1990; 86 1991-1998
- 44 Tuma D J, Todero S L, Barak-Bernhagen M, Sorrell M F. Effects of chronic ethanol administration on the endocytosis of cytokines by rat hepatocytes. Alcohol Clin Exp Res. 1996; 20 579-583
- 45 Xu D, Thiele G M, Beckenhauer J L et al.. Detection of circulating antibodies to malondialdehyde-acetaldehyde (MAA) adducts in ethanol-fed rats. Gastroenterology. 1997; 115 686-692
- 46 Worrall S, de Jersey J, Wilce P A. Comparison of the formation of proteins modified by direct and indirect ethanol metabolites in the liver and blood of rats fed the Lieber-DeCarli liquid diet. Alcohol Alcohol. 2000; 35 164-170
- 47 Thiele G M, Tuma D J, Willis M S et al.. Soluble proteins modified with acetaldehyde and malondialdehyde are immunogenic in the absence of adjuvant. Alcohol Clin Exp Res. 1998; 22 1731-1739
- 48 Albano E, Tomasi A, Goria-Gatti L, Dianzani M U. Spin trapping of free radical species produced during the microsomal metabolism of ethanol. Chem Biol Interact. 1988; 65 223-234
- 49 Albano E, Parola M, Comoglio A, Dianzani M U. Evidence for the covalent binding of HERs to rat liver microsomal proteins. Alcohol Alcohol. 1993; 28 453-459
- 50 Thiele G M, Miller J A, Klassen L W, Tuma D J. Long-term ethanol administration alters the degradation of acetaldehyde adducts by liver endothelial cells. Hepatology. 1996; 24 643-648
- 51 Thiele G M, Miller J A, Klassen L W, Tuma D J. Chronic ethanol consumption impairs receptor-mediated endocytosis of formaldehyde-treated albumin by isolated rat liver endothelial cells. Hepatology. 1999; 29 1511-1517
- 52 Duryee M J, Klassen L W, Freeman T L et al.. Chronic ethanol consumption impairs receptor-mediated endocytosis of MAA-modified albumin by liver endothelial cells. Biochem Pharmacol. 2003; 66 1045-1054
- 53 Kharbanda K K, Todero S L, Shubert K A, Sorrell M F, Tuma D J. Malondialdehyde-acetaldehyde-protein adducts increase secretion of chemokines by rat hepatic stellate cells. Alcohol. 2001; 25 123-128
- 54 Thiele G M, Duryee M J, Willis M S et al.. Malondialdehyde-acetaldehyde (MAA) modified proteins induce pro-inflammatory and pro-fibrotic responses by liver endothelial cells. Comp Hepatol. 2004; 3(Suppl 1) S25
- 55 Behrens U J, Paronetto F. Studies on “liver-specific” antigens. I. Evaluation of the liver specificity of “LSP” and “LP-2”. Gastroenterology. 1979; 77 1045-1052
- 56 McFarlane I G, Wojcicka B M, Williams R. Antigens of the human liver. Clin Exp Immunol. 1980; 40 1-7
- 57 Manns M, Meyer zum Buschenfelde K H, Hess G. Autoantibodies against liver-specific membrane lipoprotein in acute and chronic liver diseases: studies on organ-, species-, and disease- specificity. Gut. 1980; 21 955-961
- 58 Perperas A, Tsantoulas D, Portmann B, Eddleston A L, Williams R. Autoimmunity to a liver membrane lipoprotein and liver damage in alcoholic liver disease. Gut. 1981; 22 149-152
- 59 Burt A D, Anthony R S, Hislop W S, Bouchier I A, MacSween R N. Liver membrane antibodies in alcoholic liver disease: 1. prevalence and immunoglobulin class. Gut. 1982; 23 221-225
- 60 Wiedmann K H, Bartholemew T C, Brown D J, Thomas H C. Liver membrane antibodies detected by immunoradiometric assay in acute and chronic virus-induced and autoimmune liver disease. Hepatology. 1984; 4 199-204
- 61 Vidali M, Stewart S F, Rolla R et al.. Genetic and epigenetic factors in autoimmune eactions toward cytochrome P4502E1 in alcoholic liver disease. Hepatology. 2003; 37 410-419
- 62 Moncada C, Torres V, Varghese G, Albano E, Israel Y. Ethanol-derived immunoreactive species formed by free radical mechanisms. Mol Pharmacol. 1994; 46 786-791
- 63 Clot P, Parola M, Bellomo G et al.. Role of plasma membrane HER adducts in causing antibody-dependent cytotoxicity in hepatocytes exposed to alcohol. Hepatology. 1995; 22 227A
- 64 Dupont I, Lucas D, Clot P, Menez C, Albano E. Cytochrome P4502E1 inducibility and HER formation among alcoholics. J Hepatol. 1998; 28 564-571
- 65 Clot P, Parola M, Bellomo G et al.. Plasma membrane HER adducts cause antibody-dependent cytotoxicity in rat hepatocytes exposed to alcohol. Gastroenterology. 1997; 113 265-276
- 66 Shimada S, Yamauchi M, Takamatsu M et al.. Experimental studies on the relationship between immune responses and liver damage induced by ethanol after immunization with homologous acetaldehyde adducts. Alcohol Clin Exp Res. 2002; 26(Suppl 8) 86S-90S
- 67 Klassen L W, Thiele G M. Immune reactivity to proteins biotransformed by alcohol metabolites. Alcohol Clin Exp Res. 1998; 22(Suppl 5) 204S-207S
- 68 Skog O J. The wetness of drinking cultures: a key variable in epidemiology of alcoholic liver cirrhosis. Acta Med Scand Suppl. 1985; 703 157-184
- 69 Lelbach W K. Cirrhosis in the alcoholic and its relation to the volume of alcohol abuse. Ann N Y Acad Sci. 1975; 252 85-105
- 70 Lelbach W K. Epidemiology of alcoholic liver disease. Prog Liver Dis. 1976; 5 494-515
- 71 Campbell R D, Milner C M. MHC genes in autoimmunity. Curr Opin Immunol. 1993; 5 887-893
- 72 Morgan M Y, Ross M G, Ng C M et al.. HLA-B8, immunoglobulins, and antibody responses in alcohol-related liver disease. J Clin Pathol. 1980; 33 488-492
- 73 Melendez M, Vargas-Tank L, Fuentes C et al.. Distribution of HLA histocompatibility antigens, ABO blood groups and Rh antigens in alcoholic liver disease. Gut. 1979; 20 288-290
- 74 Bell H, Nordhagen R. Association between HLA-BW40 and alcoholic liver disease with cirrhosis. BMJ. 1978; 1 822
- 75 Bell H, Nordhagen R. HLA antigens in alcoholics, with special reference to alcoholic cirrhosis. Scand J Gastroenterol. 1980; 15 453-456
- 76 Scott B B, Rajah S M, Losowsky M S. Histocompatibility antigens in chronic liver disease. Gastroenterology. 1977; 72 122-125
- 77 Simon M, Bourel M, Genetet B et al.. Idiopathic hemochromatosis and iron overload in alcoholic liver disease: differentiation by HLA phenotype. Gastroenterology. 1977; 73 655-658
- 78 Wilkinson P, Santamaria J N, Rankin J G. Epidemiology of alcoholic cirrhosis. Australas Ann Med. 1969; 18 222-226
- 79 Krasner N, Davis M, Portmann B, Williams R. Changing pattern of alcoholic liver disease in Great Britain: relation to sex and signs of autoimmunity. BMJ. 1977; 1 1497-1500
- 80 Morgan M Y, Sherlock S. Sex-related differences among 100 patients with alcoholic liver disease. BMJ. 1977; 1 939-941
- 81 Tuyns A J, Pequignot G. Greater risk of ascitic cirrhosis in females in relation to alcohol consumption. Int J Epidemiol. 1984; 13 53-57
- 82 Saunders J B, Wodak A D, Haines A et al.. Accelerated development of alcoholic cirrhosis in patients with HLA-B8. Lancet. 1982; 1 1381-1384
- 83 Prytz H, Skinhoj P. Morbidity, mortality, and incidence of cirrhosis in Denmark 1976-1978. Scand J Gastroenterol. 1981; 16 839-844
- 84 Bounds W, Betzing K W, Stewart R M, Holcombe R F. Social drinking and the immune response: impairment of lymphokine-activated killer activity. Am J Med Sci. 1994; 307 391-395
- 85 Chiappelli F, Kung M, Lee P et al.. Alcohol modulation of human normal T-cell activation, maturation, and migration. Alcohol Clin Exp Res. 1995; 19 539-544
- 86 Degos F, Duhamel G, Brechot C et al.. Hepatitis B vaccination in chronic alcoholics. J Hepatol. 1986; 2 402-409
- 87 Watson R R, Borgs P, Witte M et al.. Alcohol, immunomodulation, and disease. Alcohol Alcohol. 1994; 29 131-139
- 88 Peterson J D, Vasquez K, Waltenbaugh C. Interleukin-12 therapy restores cell-mediated immunity in ethanol-consuming mice. Alcohol Clin Exp Res. 1998; 22 245-251
- 89 Uchimura Y, Sata M, Kage M, Abe H, Tanikawa K. A histopathological study of alcoholics with chronic HCV infection: comparison with chronic hepatitis C and alcoholic liver disease. Liver. 1995; 15 300-306
- 90 Tamai T, Seki T, Shiro T et al.. Effects of alcohol consumption on histological changes in chronic hepatitis C: a clinicopathological study. Alcohol Clin Exp Res. 2000; 24(Suppl 4) 106S-111S
- 91 Mufti S I, Prabhala R, Moriguchi S, Sipes I G, Watson R R. Functional and numerical alterations induced by ethanol in the cellular immune system. Immunopharmacology. 1988; 15 85-93
- 92 Szabo G, Mandrekar P, Dolganiuc A, Catalano D, Kodys K. Reduced alloreactive T-cell activation after alcohol intake is due to impaired monocyte accessory cell function and correlates with elevated IL-10, IL-13, and decreased IFNgamma levels. Alcohol Clin Exp Res. 2001; 25 1766-1772
- 93 Tsai S L, Liaw Y F, Chen M H, Huang C Y, Kuo G C. Detection of type 2-like T-helper cells in hepatitis C virus infection: implications for hepatitis C virus chronicity. Hepatology. 1997; 25 449-458
- 94 Fukui H, Brauner B, Bode J C, Bode C. Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay. J Hepatol. 1991; 12 162-169
- 95 Bode C, Kugler V, Bode J C. Endotoxemia in patients with alcoholic and non-alcoholic cirrhosis and in subjects with no evidence of chronic liver disease following acute alcohol excess. J Hepatol. 1987; 4 8-14
- 96 Stern M, Carter E A, Walker W A. Food proteins and gut mucosal barrier. IV. Effects of acute and chronic ethanol administration on handling and uptake of bovine serum albumin by rat small intestine. Dig Dis Sci. 1986; 31 1242-1248
- 97 Parlesak A, Schafer C, Schutz T, Bode J C, Bode C. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. J Hepatol. 2000; 32 742-747
- 98 Urbaschek R, McCuskey R S, Rudi V et al.. Endotoxin, endotoxin-neutralizing-capacity, sCD14, sICAM-1, and cytokines in patients with various degrees of alcoholic liver disease. Alcohol Clin Exp Res. 2001; 25 261-268
- 99 Thurman R G. II. Alcoholic liver injury involves activation of Kupffer cells by endotoxin. Am J Physiol. 1998; 275 G605-G611
- 100 Adachi Y, Bradford B U, Gao W, Bojes H K, Thurman R G. Inactivation of Kupffer cells prevents early alcohol-induced liver injury. Hepatology. 1994; 20 453-460
- 101 Jarvelainen H A, Fang C, Ingelman-Sundberg M et al.. Kupffer cell inactivation alleviates ethanol-induced steatosis and CYP2E1 induction but not inflammatory responses in rat liver. J Hepatol. 2000; 32 900-910
- 102 Mezey E. Alcoholic liver disease. Prog Liver Dis. 1982; 7 555-572
- 103 French S W, Burbige E J. Alcoholic hepatitis: clinical, morphologic, pathogenic, and therapeutic aspects. Prog Liver Dis. 1979; 6 557-579
- 104 Bhagwandeen B S, Apte M, Manwarring L, Dickeson J. Endotoxin induced hepatic necrosis in rats on an alcohol diet. J Pathol. 1987; 152 47-53
- 105 Arai M, Nakano S, Okuno F et al.. Endotoxin-induced hypercoagulability: a possible aggravating factor of alcoholic liver disease. Hepatology. 1989; 9 846-851
- 106 Honchel R, Ray M B, Marsano L et al.. Tumor necrosis factor in alcohol enhanced endotoxin liver injury. Alcohol Clin Exp Res. 1992; 16 665-669
- 107 Hoffmann R, Grewe M, Estler H C, Schulze-Specking A, Decker K. Regulation of tumor necrosis factor-alpha-mRNA synthesis and distribution of tumor necrosis factor-alpha-mRNA synthesizing cells in rat liver during experimental endotoxemia. J Hepatol. 1994; 20 122-128
- 108 Thiele G M, Klassen L W, Miller J A, Hill G E, Tuma D J. Binding of aldehyde-modified proteins to liver endothelial cells changes the adhesion molecule and TNF-alpha Expression. J Allergy Clin Immunol. 1997; 99 S195
- 109 Nanji A A, Zhao S, Sadrzadeh S M, Waxman D J. Use of reverse transcription-polymerase chain reaction to evaluate in vivo cytokine gene expression in rats fed ethanol for long periods. Hepatology. 1994; 19 1483-1487
- 110 McClain C J, Cohen D A. Increased tumor necrosis factor production by monocytes in alcoholic hepatitis. Hepatology. 1998; 9 349-351
- 111 Felver M E, Mezey E, McGuire M et al.. Plasma tumor necrosis factor alpha predicts decreased long-term survival in severe alcoholic hepatitis. Alcohol Clin Exp Res. 1990; 14 255-259
- 112 Bird G L, Sheron N, Goka A K, Alexander G J, Williams R S. Increased plasma tumor necrosis factor in severe alcoholic hepatitis. Ann Intern Med. 1990; 112 917-920
- 113 Shiratori Y, Takada H, Hikiba Y et al.. Production of chemotactic factor, interleukin-8, from hepatocytes exposed to ethanol. Hepatology. 1993; 18 1477-1482
- 114 Van Zee K J, Fischer E, Hawes A S et al.. Effects of intravenous IL-8 administration in nonhuman primates. J Immunol. 1992; 148 1746-1752
- 115 Hill D B, Marsano L S, McClain C J. Increased plasma interleukin-8 concentrations in alcoholic hepatitis. Hepatology. 1993; 18 576-580
- 116 Sheron N, Bird G, Koskinas J et al.. Circulating and tissue levels of the neutrophil chemotaxin interleukin-8 are elevated in severe acute alcoholic hepatitis, and tissue levels correlate with neutrophil infiltration. Hepatology. 1993; 18 41-46
- 117 Khoruts A, Stahnke L, McClain C J, Logan G, Allen J I. Circulating tumor necrosis factor, interleukin-1 and interleukin-6 concentrations in chronic alcoholic patients. Hepatology. 1991; 13 267-276
- 118 McClain C J, Cohen D A, Dinarello C A et al.. Serum interleukin-1 (IL-1) activity in alcoholic hepatitis. Life Sci. 1986; 39 1479-1485
- 119 Deviere J, Content J, Denys C et al.. Excessive in vitro bacterial lipopolysaccharide-induced production of monokines in cirrhosis. Hepatology. 1990; 11 628-634
- 120 Kishimoto T. The biology of interleukin-6. Blood. 1989; 74 1-10
- 121 Deviere J, Content J, Denys C et al.. High interleukin-6 serum levels and increased production by leucocytes in alcoholic liver cirrhosis. Correlation with IgA serum levels and lymphokines production. Clin Exp Immunol. 1989; 77 221-225
- 122 Hill D B, Marsano L, Cohen D et al.. Increased plasma interleukin-6 concentrations in alcoholic hepatitis. J Lab Clin Med. 1992; 119 547-552
- 123 McClain C, Hill D, Schmidt J, Diehl A M. Cytokines and alcoholic liver disease. Semin Liver Dis. 1993; 13 170-182
- 124 Ulich T R, Guo K, del Castillo J. Endotoxin-induced cytokine gene expression in vivo. I. Expression of tumor necrosis factor mRNA in visceral organs under physiologic conditions and during endotoxemia. Am J Pathol. 1989; 134 11-14
- 125 Peristeris P, Clark B D, Gatti S et al.. N-acetylcysteine and glutathione as inhibitors of tumor necrosis factor production. Cell Immunol. 1992; 140 390-399
- 126 Deaciuc I V, Alappat J M, D’Souza N B. Effect of acute and chronic alcohol administration to rats on the expression of interleukin-6 cell-surface receptors of hepatic parenchymal and nonparenchymal cells. Alcohol Clin Exp Res. 1994; 18 1207-1214
- 127 Mills P R, Shenkin A, Anthony R S et al.. Assessment of nutritional status and in vivo immune responses in alcoholic liver disease. Am J Clin Nutr. 1983; 38 849-859
- 128 Calvey H, Davis M, Williams R. Controlled trial of nutritional supplementation, with and without branched chain amino acid enrichment, in treatment of acute alcoholic hepatitis. J Hepatol. 1985; 1 141-151
- 129 Thestrup-Pedersen K, Ladefoged K, Andersen P. Lymphocyte transformation test with liver-specific protein and phytohaemagglutinin in patients with liver disease. Clin Exp Immunol. 1976; 24 1-8
- 130 Young G P, Dudley F J, Van Der Weyden M B. Suppressive effect of alcoholic liver disease sera on lymphocyte transformation. Gut. 1979; 20 833-839
- 131 Pelletier G, Segond P, Attali P, Briantais M J, Etienne J P. Phenotype study of blood T lymphocytes in alcoholic hepatopathies. Gastroenterol Clin Biol. 1984; 8 911-924
- 132 Perrin D, Bignon J D, Beaujard E, Cheneau M L. Populations of circulating T lymphocytes in patients with alcoholic cirrhosis. Gastroenterol Clin Biol. 1984; 8 907-910
- 133 Couzigou P, Vincendeau P, Fleury B et al.. Changes in circulating lymphocyte subsets in alcoholic hepatopathies. Respective role of alcohol, hepatocellular insufficiency and malnutrition. Gastroenterol Clin Biol. 1984; 8 915-919
- 134 Watson R R, Jackson J C, Hartmann B et al.. Cellular immune functions, endorphins, and alcohol consumption in males. Alcohol Clin Exp Res. 1985; 9 248-254
- 135 Si L, Whiteside T L, Schade R R, Van Thiel D. Lymphocyte subsets studied with monoclonal antibodies in liver tissues of patients with alcoholic liver disease. Alcohol Clin Exp Res. 1983; 7 431-435
- 136 Muller C, Wolf H, Gottlicher J, Eibl M M. Helper-inducer and suppressor-inducer lymphocyte subsets in alcoholic cirrhosis. Scand J Gastroenterol. 1991; 26 295-301
- 137 Van Epps E, Husby G, Williams Jr R C, Strickland R G. Liver disease-a prominent cause of serum IgE elevation. Clin Exp Immunol. 1976; 23 444-450
- 138 Iturriaga H, Pereda T, Estevez A, Ugarte G. Serum immunoglobulin A changes in alcoholic patients. Ann Clin Res. 1977; 9 39-43
- 139 Sorrell M F. Leevy CM. Lymphocyte transformation and alcoholic liver injury. Gastroenterology. 1972; 63 1020-1025
- 140 Zetterman R K, Leevy C M. Immunologic reactivity and alcoholic liver disease. Bull N Y Acad Med. 1975; 51 533-544
- 141 Zetterman R K, Luisada-Opper A. LEEVY CM. Alcoholic hepatitis. Cell-mediated immunological response to alcoholic hyalin. Gastroenterology. 1976; 70 382-384
- 142 Johnson R D, Williams R. Immune responses in alcoholic liver disease. Alcohol Clin Exp Res. 1986; 10 471-486
- 143 Izumi N, Hasumura Y, Takeuchi J. Lymphocyte cytotoxicity for autologous human hepatocytes in alcoholic liver disease. Clin Exp Immunol. 1983; 54 219-224
- 144 Poralla T, Hutteroth T H, Meyer zum Buschenfelde K H. Cellular cytotoxicity against autologous hepatocytes in alcoholic liver disease. Liver. 1984; 4 117-121
- 145 Anthony R S, Farquharson M, MacSween R N. Liver membrane antibodies in alcoholic liver disease. II. Antibodies to ethanol-altered hepatocytes. J Clin Pathol. 1983; 36 1302-1308
- 146 Neuberger J, Crossley I R, Saunders J B et al.. Antibodies to alcohol altered liver cell determinants in patients with alcoholic liver disease. Gut. 1984; 25 300-304
- 147 Izumi N, Sato C, Hasumura Y, Takeuchi J. Serum antibodies against alcohol-treated rabbit hepatocytes in patients with alcoholic liver disease. Clin Exp Immunol. 1985; 61 585-952
- 148 Niemela O, Parkkila S, Yla-Herttuala S et al.. Covalent protein adducts in the liver as a result of ethanol metabolism and lipid peroxidation. Lab Invest. 1994; 70 537-546
- 149 Tuma D J, Thiele G M, Xu D, Klassen L W, Sorrell M F. Acetaldehyde and malondialdehyde react together to generate distinct protein adducts in the liver during long-term ethanol administration. Hepatology. 1996; 23 872-880
- 150 Albano E, Tomasi A, Persson J O et al.. Role of ethanol-inducible cytochrome P450 (P450IIE1) in catalysing the free radical activation of aliphatic alcohols. Biochem Pharmacol. 1991; 41 1895-1902
- 151 Clot P, Bellomo G, Tabone M, Arico S, Albano E. Detection of antibodies against proteins modified by hydroxyethyl free radicals in patients with alcoholic cirrhosis. Gastroenterology. 1995; 108 201-207
Geoffrey M ThielePh.D.
University of Nebraska Medical Center, Department of Internal Medicine, Section of
Rheumatology and Immunology
983025 Nebraska Medical Center
Omaha, NE 68198-3025
Email: gthiele@unmc.edu