title: Lipid peroxidation and serum cytokines in acute alcoholic hepatitis.
abstract: OBJECTIVE
  Increased exposure of Kupffer cells to intestinal-borne Gram-negative bacteria enhances the metabolism and leads to cytokine production by these cells. Activation of Kupffer cells increases free radical release, which may, in turn, enhance cytokine secretion, creating a positive feedback loop, which contributes to liver inflammation. Cytokines act on T cells, inducing their proliferation and secretion of additional interleukins. Lipid peroxidation products (malondialdehyde; MDA) form adducts with proteins and acetaldehyde, triggering a T cell immune response. Controversy exists about the predominance of either Th-1 or Th-2 cellular responses. We performed the present study in order to analyse the cytokine pattern in patients with acute alcoholic hepatitis, its relation to MDA and the relation between all these parameters and liver function and prognosis.
  
  
  METHODS
  The study included 53 male alcoholics, 47 followed up for a median time of 32 months, during which 17 of them died. We measured serum MDA, tumour necrosis factor-alpha, interferon gamma (IFNG) and interleukins (IL) 4, 6, 8, and 10.
  
  
  RESULTS
  MDA levels were raised in cirrhotics and non-cirrhotics with alcoholic hepatitis, maintaining a relationship with bilirubin and Maddrey index, and with mortality in the univariate analysis. Both IFNG and IL-4 were raised in our patients compared with controls, as well as IL-8, and IL-6, but IL-10 were below the detection limit in the majority of cases, especially in cirrhotics. Using a Cox regression model, Maddrey index displaced MDA in the survival analysis.
  
  
  CONCLUSIONS
  Our data lend support to the hypothesis that activation of both Th-1 and Th-2 cell subsets take place. MDA levels are raised in alcoholics with alcoholic hepatitis and are closely related to liver function derangement and to survival, although this is displaced by Maddrey index using Cox regression model.
authors.affiliation: Servicio de Medicina, Interna' Hospital Universitario, Ofra s/n, Tenerife, Canary Islands, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Sánchez Pérez
authors.forename: Emilio
authors.initials: E
authors.lastname: González-Reimers
authors.forename: Francisco
authors.initials: F
authors.lastname: Santolaria-Fernández
authors.forename: María José
authors.initials: MJ
authors.lastname: de la Vega-Prieto
authors.forename: Antonio
authors.initials: A
authors.lastname: Martínez-Riera
authors.forename: Pedro Abreu
authors.initials: PA
authors.lastname: González
authors.forename: Eva
authors.initials: E
authors.lastname: Rodríguez Rodríguez
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Durán-Castellón
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D001663:Bilirubin / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood*; D005609:Free Radicals / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000302:isolation & purification; D006519:Hepatitis, Alcoholic / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism / Q000382:microbiology; D015227:Lipid Peroxidation / Q000502:physiology*; D008099:Liver / Q000378:metabolism / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000097:blood / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D013997:Time Factors
chemical_list: D016207:Cytokines; D005609:Free Radicals; D008315:Malondialdehyde; D001663:Bilirubin