Gene expression of tumor necrosis factor α and TNF‐receptors, p55 and p75, in nonalcoholic steatohepatitis patients

The main objective of this study was to analyze the pathogenic role of the tumor necrosis factor α (TNF‐α) system in the development of nonalcoholic steatohepatitis (NASH). Fifty‐two obese patients were studied. We investigated: (1) the expression of mRNA of TNF‐α and their p55 and p75‐receptors by quantitative reverse‐transcriptase polymerase chain reaction (RT‐PCR) in hepatic and adipose tissues; and (2) the relationship between TNF‐α, p55, and p75 and the severity of NASH. Obese patients without NASH were the control group. A remarkable increase in the expression of mRNA of TNF‐α was found in patients with NASH in hepatic tissue (0.65 ± 0.54) and in peripheral fat (0.43 ± 0.45); in the control samples, the mRNA expression was 0.28 ± 0.32, P < .007, and 0.26 ± 0.22, P < .018, respectively. Furthermore, we found a significant increase in the mRNA levels of p55 receptor (2.42 ± 1.81 vs. 1.56 ± 1.17; P < .05); however, the mRNA expression of the p75 receptor was similar in both patients. Those patients with NASH with significant fibrosis presented an increase in the expression of mRNA TNF‐α in comparison with those with a slight or nonexistent fibrosis. An overexpression of TNF‐α mRNA is found in the liver and in the adipose tissue of NASH patients. The levels of mRNA‐p55 are increased in the liver tissue of NASH patients. This overexpression is more elevated in patients with more advanced NASH. These findings suggest that the TNF‐α system may be involved in the pathogenesis of NASH.