We evaluated the expression of interleukin-la, interleukin-18, tumor necrosis factor-a and transforming growth factor-8 mRNAs in the intragastric-feeding rat model of alcoholic liver disease. Rats were fed different diets for periods of 2 or 4 wk. Animals fed saturated fat and ethanol and the corn oil-dextrose control group had no liver injury, whereas animals fed corn oil and ethanol showed pathologic changes. RNA was extracted from the livers at the time of killing, reversetranscribed and amplified; polymerase chain reaction products were subjected to electrophoresis on agarose gel. Interleukin-la mRNA was present in all groups at 2 and 4 wk; interleukin-lp and transforming growth factor-p mRNAs were present in all groups at 4 wk. Tumor necrosis factor-ol mRNA was absent in all groups at 2 wk but was present in the corn oil-ethanol group only at 4 wk. Because pathological liver injury was evident in the corn oil-ethanol group by 4 wk, the presence of tumor necrosis factor-a mRNA at this time suggests a pathogenetic role for tumor necrosis factor-a in alcohol-induced liver injury. (HEPATOLOGY 1994; 19: 1483-1487.)
Many of the features of alcoholic liver disease are associated with the acute-phase response, which includes fever, malaise, anorexia and leukocytosis (1, 2). This response has been attributed to the production of a variety of peptides by monocytes and monocytederived cells, including the Kupffer cells in the hepatic sinusoids (3, 4). These peptides include tumor necrosis factor-a (TNF-a), interleukin-la (IL-la), interleukin-1 P (IL-1p) and transforming growth factor-p (TGF-P) (5).
Several studies have indicated a correlation between circulating levels of macrophage-derived cytokines and disease progression in alcoholic liver disease (6-8). Increased plasma levels of TNF correlate with decreased long-term survival in patients with alcoholic hepatitis (6). McClain and Cohen have shown that spontaneous