INDOMETHACIN ENHANCES SERUM 2'5'-OLIGOADENYLATE SYNTHETASE IN PATIENTS WITH HEPATITIS-B AND HEPATITIS-C VIRUS CHRONIC ACTIVE HEPATITIS

Activation of the arachidonic acid metabolism seems to be one of the p ost-receptor mechanisms by which interferon-alpha induces antiviral pr otein synthesis. In this study, we evaluated the changes on serum 2'5' -oligoadenylate synthetase levels induced by acute administration of i nterferon-alpha, indomethacin and interferon-a plus indomethacin in 21 patients with hepatitis B or C virus chronic active hepatitis. Serum samples for 2'5'-oligoadenylate synthetase determination were collecte d in basal conditions and 8 h after the administration of interferon-a lpha, indomethacin and interferon-alpha plus indomethacin. Compared to control value (mean +/- SE) (40.2 +/- 7.9 pg/dl) serum 2'5'-oligoaden ylate synthetase concentration was significantly increased 1.5-fold af ter interferon-alpha (63.4 +/- 11, p<0.001), 2.8-fold after indomethac in (115.5 +/- 21, p<0.001) and 3.7-fold after interferon-alpha plus in domethacin (148.9 +/- 25.1, p<0.001). When patients with different vir al infections were considered separately, basal 2'5'-oligoadenylate sy nthetase concentrations were similar in both HBeAg and HBeAb-positive patients, but about 2-fold higher in hepatitis C virus. Compared to th e control value, interferon-alpha caused a 1.5-fold increase in HBeAg- and hepatitis C virus-positive and a 2-fold increase in HBeAb-positiv e patients. Indomethacin led to a 1.8-fold increase in HBeAg, a 2-fold increase in hepatitis C virus-positive and surprisingly a 6.8-fold in crease in HBeAb-positive patients. Simultaneous administration of the two drugs had an additive effect on the 2'5'-oligoadenylate synthetase increase in HBeAg-positive (2.4-fold increase) and a synergistic effe ct in hepatitis C virus- and HBeAb-positive patients (2.7- and 10.2-fo ld increase, respectively). Apart from confirming the interaction betw een arachidonic acid metabolites and interferon-alpha, the results of this study suggest both an altered antiviral response to interferon-al pha in viral chronic active hepatitis and the possibility that nonster oid anti-inflammatory drugs can enhance the antiviral activity of inte rferon-alpha. We conclude that the association of interferon-alpha wit h nonsteroid anti-inflammatory drugs in patients with chronic viral he patitis, who are non-responders to interferon-alpha alone, should be e valuated, taking into account the possible side effects of nonsteroid anti-inflammatory drugs. (C) Journal of Hepatology.