Lipid peroxidation contributes to immune reactions associated with alcoholic liver disease.
Increasing evidence indicates the involvement of immune reactions in the pathogenesis of alcoholic liver disease. We have investigated whether ethanol-induced oxidative stress might contribute to immune response in alcoholics. Antibodies against human serum albumin modified by reaction with malondialdehyde (MDA), 4-hydroxynonenal (HNE), 2-hexenal, acrolein, methylglyoxal, and oxidized arachidonic and linoleic acids were measured by ELISA in 78 patients with alcoholic cirrhosis and/or hepatitis, 50 patients with nonalcoholic cirrhosis, 23 heavy drinkers with fatty liver, and 80 controls. Titers of IgG-recognizing epitopes derived from MDA, HNE, and oxidized fatty acids were significantly higher in alcoholic as compared to nonalcoholic cirrhotics or healthy controls. No differences were instead observed in the titers of IgG-recognizing acrolein-, 2-hexenal-, and methylglyoxal-modified albumin. Alcoholics showing high IgG titers to one adduct tended to have high titers to all the others. However, competition experiments showed that the antigens recognized were structurally unrelated. Anti-MDA and anti-HNE antibodies were significantly higher in cirrhotics with more severe disease as well as in heavy drinkers with cirrhosis or extensive fibrosis than in those with fatty liver only. We conclude that antigens derived from lipid peroxidation contribute to the development of immune responses associated with alcoholic liver disease.
Mottaran
Elisa
E
Department of Medical Sciences, Amedeo Avogadro University of East Piedmont, Via Solaroli 17, 28100 Novara, Italy.
Stewart
Stephen F
SF
Rolla
Roberta
R
Vay
Daria
D
Cipriani
Valentina
V
Moretti
MariaGrazia
M
Vidali
Matteo
M
Sartori
Massimo
M
Rigamonti
Cristina
C
Day
Christopher P
CP
Albano
Emanuele
E
D000171:Acrolein / Q000737:chemistry / Q000276:immunology; D000328:Adult; D000368:Aged; D000447:Aldehydes / Q000737:chemistry / Q000276:immunology; D016718:Arachidonic Acid / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D019787:Linoleic Acid / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015227:Lipid Peroxidation / Q000276:immunology*; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000276:immunology*; D008297:Male; D008315:Malondialdehyde / Q000737:chemistry / Q000276:immunology; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D012709:Serum Albumin / Q000737:chemistry / Q000276:immunology
D000447:Aldehydes; D007074:Immunoglobulin G; D012709:Serum Albumin; D016718:Arachidonic Acid; D000431:Ethanol; D008315:Malondialdehyde; D000171:Acrolein; D019787:Linoleic Acid; C027576:4-hydroxy-2-nonenal