Tumor necrosis factor a (TNF-a) is a cytokine with infectious agents and has been shown to exert direct pleiotropic properties that is induced in a variety of antiviral effects. [3][4][5] Although low levels of TNF-a can pathological situations including viral infections. In this contribute to cell protection, excessive amounts may work, we analyzed the expression of TNF-a gene in pacause cell damage. 2,6 tients with chronic hepatitis C. Serum TNF-a levels were
The biosynthesis of TNF-a is tightly regulated by found to be elevated in all chronic hepatitis C patients transcriptional and post-transcriptional mechanisms. 1 including those cases presenting sustained biochemical A variety of viruses have been shown to induce the remission of the disease after interferon therapy. Unexpression of TNF-a in vitro. [6][7][8][9] The accumulation of treated patients with chronic hepatitis C showed in-TNF-a messenger RNA (mRNA) that occur in viruscreased TNF-a messenger RNA (mRNA) levels in the liver and mononuclear cells as compared with healthy infected cells 6,8,9 may result from both increased trancontrols. After completion of treatment with interferon, scription and stabilization of the transcripts. 8 Accumupatients experiencing sustained complete response lation of TNF-a mRNA primes the cell for enhanced showed values of TNF-a mRNA, both in the liver and in release of bioactive TNF-a in response to other inperipheral mononuclear cells, within the normal range, ducers such as cytokines, C5a, or bacterial products. 1,8 significantly lower than patients who did not respond to TNF-a has been involved in the pathogenesis of a interferon and than those with complete response who diversity of liver conditions including viral hepatirelapsed after interferon withdrawal. Pretreatment valtis. [10][11][12][13][14][15][16][17][18] Increased production of TNF-a by peripheral ues of TNF-a mRNA were lower in long-term responders to interferon than in cases who failed to respond to the blood mononuclear cells (PBMC) has been observed in treatment. Values of TNF-a mRNA in the liver or in fulminant viral hepatitis, 17 in chronic hepatitis B and mononuclear cells were higher in specimens with posiin chronic non-A non-B hepatitis. 16,18 Recently, raised tive hepatitis C virus (HCV) RNA than in those samples serum TNF-a levels have been shown in chronic hepatiwhere the virus was undetectable. Neither the intensity tis C virus (HCV) infection. 19 of the liver damage nor the amount of HCV RNA in se-HCV is a single-stranded RNA virus that infects both rum or in cells showed correlation with the levels of the liver and lymphoid cells. [20][21][22] HCV infection has a TNF-a transcripts in peripheral mononuclear cells but strong tendency to chronicity and constitutes a very it was found that high TNF-a values were associated with genotype 1b. In conclusion, there is an enhanced common cause of chronic liver disease in the western expression of TNF-a in HCV infection. High levels of this world. Thus far, interferon alfa (IFN-a) is the most cytokine may play a role in the resistance to interferon effective antiviral agent in chronic hepatitis C. Howtherapy. (HEPATOLOGY 1996;23:210-217.) ever, only about 50% of the treated patients respond to IFN-a therapy with normalization of serum trans-Tumor necrosis factor a (TNF-a) is a cytokine, proaminases, and half of these patients relapse after interduced primarily by activated monocytes and lymphoruption of the treatment. 23 cytes, that possesses pleiotropic properties. 1,2 It partici-Little is known about the mechanisms determining pates in the induction of the immune response to the severity of the liver damage and the response to IFN-a in HCV infection. In this paper, we have studied Abbreviations: TNF-a, tumor necrosis factor a; mRNA, messenger RNA; the levels of TNF-a in serum, TNF-a transcripts in the PBMC, peripheral blood mononuclear cells; HCV, hepatitis C virus; IFN-a, liver and PBMC in patients with chronic hepatitis C interferon alfa; UT, untreated group; SR, sustained response; Rr, response and the relationship between this cytokine and the rewith relapse; NR, no response; ALT, alanine aminotransferase; ELISA, enzyme-linked immunosorbent assay; RT-PCR, reverse transcriptase-polymer-sponse to IFN-a treatment. Our results indicate that ase chain reaction; cDNA, complementary DNA.