Activity of the interferon-induced 2',5'-oligoadenylate synthetase in patients with chronic hepatitis C.

Abstract

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.

• Authors: J M Pawlotsky, A Hovanessian, F Roudot-Thoraval, P Lebon, N Robert, M Bouvier, G Babany, J Duval, D Dhumeaux
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 15 Issue 10 Pg. 857-62 (Oct 1995) ISSN: 1079-9907 [Print] United States
• PMID: 8564707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• 2',5'-Oligoadenylate Synthetase

Topics

• 2',5'-Oligoadenylate Synthetase (biosynthesis)
• Adult
• Case-Control Studies
• Chronic Disease
• Enzyme Induction
• Female
• Hepatitis C (blood, enzymology)
• Humans
• Interferon alpha-2
• Interferon-alpha (blood, pharmacology)
• Leukocytes, Mononuclear (drug effects, enzymology)
• Male
• Middle Aged
• Recombinant Proteins