Indomethacin increases 2′,5′-oligoadenylate synthetase release by cultured liver tissue of patients with HCV chronic active hepatitis

Interferon-α (IFN-α) stimulates the synthesis of antiviral proteins, such as 2′,5′-oligoadenylate synthetase (2′5′-OAS), and activation of arachidonic acid (AA) metabolism seems to constitute the post-receptorial signal induced by this cytokine. We evaluated the in vitro effect of IFN-α, indomethacin (an inhibitor of cyclooxygenase pathway of AA) and IFN-α plus indomethacin on 2′5′-OAS release by cultured liver biopsies of patients with active or inactive HCV infection and uninfected patients with various liver diseases. The results demonstrated that basal 2′5′-OAS release was significantly higher in patients with active HCV infection with respect to uninfected ones. In two HCV-Ab positive but HCV-RNA negative patients, basal 2′5′-OAS was similar to uninfected patients. In HCV-RNA positive patients, indomethacin alone was able to significantly increase the 2′5′-OAS production in a similar fashion to IFN-α alone, while a synergistic effect on 2′5′-OAS increase was seen when biopsies were cultured with IFN-α plus indomethacin. A similar trend was observed in the uninfected and in the HCV-Ab positive but HCV-RNA negative patients, even if the increase did not reach statistical significance. These results confirm the interaction between IFN-α and AA metabolites and suggest an evaluation of the in vivo response of IFN-α plus nonsteroid antiinflammatory drugs combined therapy. © 1994.