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

The interferon-induced 2',5'-oligoadenylate synthetase (2-5OAS) is res ponsible, at least in part, for the antiviral state established in cel ls in response to viral infections, The purpose of this work was to st udy the relationship between hepatitis C virus (HCV) infection and 2-5 OAS in patients with chronic hepatitis C, Peripheral blood mononuclear cells (PBMC) of 27 patients with chronic hepatitis C were investigate d, as well as PBMC of 10 control subjects, Then, the patients were tre ated with 3 mu interferon-alpha(2a) three times per week, At month 3 o f 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 n mol/10(6) cells in patients versus 1.6 +/- 1.1 nmol/10(6) cells in con trols (p < 0.01), Basal in vivo 2-5OAS activity did not correlate with mean HCV viremia, quantified by a ''branched DNA''-based assay, Befor e 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 th e patients and the controls, However, in vitro induction of 2-5OAS act ivity 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 ac tivity was significantly induced (20.5 +/- 17.9; p < 0.0001), In vitro IFN inductions of 2-5OAS activity in PBMC before treatment and at mon th 3 of therapy were not significantly different. In conclusion, in vi vo 2-5OAS activity is significantly induced in patients with chronic h epatitis C, but endogenously produced interferon-alpha does not seem t o be involved, Chronic induction of 2-5OAS activity results in a decre ased sensitivity of PBMC to exogenous interferon induction, Whether th is phenomenon plays a role in the resistance of chronic hepatitis C to interferon therapy remains uncertain.