ACTIVITY OF THE INTERFERON-INDUCED 2',5'-OLIGOADENYLATE SYNTHETASE IN PATIENTS WITH CHRONIC HEPATITIS-C

The interferon-induced 2',5'-oligoadenylate synthetase (2-5OAS) is responsible, at least in part, for the antiviral state established in cells in response to viral infections, The purpose of this work was to study the relationship between hepatitis C virus (HCV) infection and 2-5OAS in patients with chronic hepatitis C, Peripheral blood mononuclear cells (PBMC) of 27 patients with chronic hepatitis C were investigated, as well as PBMC of 10 control subjects, Then, the patients were treated with 3 mu interferon-alpha(2a) three times per week, At month 3 of therapy, PBMC were sampled, Of the total PBMC samples obtained, half were used for determination of in vivo 2-5OAS activity, The remaining cells were cultured for 24 h in either the absence or presence of 500 U/ml of interferon-alpha(2a) for the determination of in vitro 2-5OAS activity, The mean basal in vivo 2-5OAS activities were 3.6 +/- 2.8 nmol/10(6) cells in patients versus 1.6 +/- 1.1 nmol/10(6) cells in controls (p < 0.01), Basal in vivo 2-5OAS activity did not correlate with mean HCV viremia, quantified by a ''branched DNA''-based assay, Before treatment, interferon-alpha was detected in the serum of 2 patients in 27, After a 24 h culture of PBMC in the presence of interferon, in vitro 2-5OAS activity was significantly induced in the PBMC of both the patients and the controls, However, in vitro induction of 2-5OAS activity was significantly lower in the PBMC of the patients than in the PBMC of the controls (p < 0.01), At month 3 therapy, in vivo 2-5OAS activity was significantly induced (20.5 +/- 17.9; p < 0.0001), In vitro IFN inductions of 2-5OAS activity in PBMC before treatment and at month 3 of therapy were not significantly different. In conclusion, in vivo 2-5OAS activity is significantly induced in patients with chronic hepatitis C, but endogenously produced interferon-alpha does not seem to be involved, Chronic induction of 2-5OAS activity results in a decreased sensitivity of PBMC to exogenous interferon induction, Whether this phenomenon plays a role in the resistance of chronic hepatitis C to interferon therapy remains uncertain.