Gene expression of tumor necrosis factor alpha 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 alpha (TNF-alpha) system in the development of nonalc oholic steatohepatitis (NASH). Fifty-two obese patients were studied. We in vestigated: (1) the expression of mRNA of TNF-alpha and their p55 and p75-r eceptors by quantitative reverse-transcriptase polymerase chain reaction (R T-PCR) in hepatic and adipose tissues, and (2) the relationship between TNF -alpha, 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-alpha 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 ex pression was 0.28 +/- 0.32, P <.007, and 0.26 +/- 0.22, P <.018, respective ly. 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 expres sion of the p75 receptor was similar in both patients. Those patients with NASH with significant fibrosis presented an increase in the expression of m RNA TNF-<alpha> in comparison with those with a slight or nonexistent fibro sis. An overexpression of TNF-alpha mRNA is found in the liver and in the a dipose tissue of NASH patients. The levels of mRNA-p55 are increased in the liver tissue of NASH patients. This overexpression is more elevated in pat ients with more advanced NASH. These findings suggest that the TNF-alpha sy stem may be involved in the pathogenesis of NASH.