Lipid peroxidation and serum cytokines in acute alcoholic hepatitis.
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.
Sánchez Pérez
M J
MJ
Servicio de Medicina, Interna' Hospital Universitario, Ofra s/n, Tenerife, Canary Islands, Spain.
González-Reimers
Emilio
E
Santolaria-Fernández
Francisco
F
de la Vega-Prieto
María José
MJ
Martínez-Riera
Antonio
A
González
Pedro Abreu
PA
Rodríguez Rodríguez
Eva
E
Durán-Castellón
M Carmen
MC
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
D016207:Cytokines; D005609:Free Radicals; D008315:Malondialdehyde; D001663:Bilirubin