Indomethacin enhances serum 2'5'-oligoadenylate synthetase in patients with hepatitis B and C virus chronic active hepatitis.
Activation of the arachidonic acid metabolism seems to be one of the post-receptor mechanisms by which interferon-alpha induces antiviral protein synthesis. In this study, we evaluated the changes on serum 2'5'-oligoadenylate synthetase levels induced by acute administration of interferon-alpha, indomethacin and interferon-alpha plus indomethacin in 21 patients with hepatitis B or C virus chronic active hepatitis. Serum samples for 2'5'-oligoadenylate synthetase determination were collected in basal conditions and 8 h after the administration of interferon-alpha, indomethacin and interferon-alpha plus indomethacin. Compared to control value (mean +/- SE) (40.2 +/- 7.9 pg/dl) serum 2'5'-oligoadenylate synthetase concentration was significantly increased 1.5-fold after interferon-alpha (63.4 +/- 11, p < 0.001), 2.8-fold after indomethacin (115.5 +/- 21, p < 0.001) and 3.7-fold after interferon-alpha plus indomethacin (148.9 +/- 25.1, p < 0.001). When patients with different viral infections were considered separately, basal 2'5'-oligoadenylate synthetase concentrations were similar in both HBeAg- and HBeAb-positive patients, but about 2-fold higher in hepatitis C virus. Compared to the control value, interferon-alpha caused a 1.5-fold increase in HBeAg- and hepatitis C virus-positive and a 2-fold increase in HBeAb-positive 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 increase 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 effect in hepatitis C virus- and HBeAb-positive patients (2.7- and 10.2-fold increase, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Andreone
P
P
Patologia Medica I, Università di Bologna, Italy.
Cursaro
C
C
Gramenzi
A
A
Buzzi
A
A
Miniero
R
R
Sprovieri
G
G
Gasbarrini
G
G
D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood*; D000293:Adolescent; D000328:Adult; D004338:Drug Combinations; D005260:Female; D006508:Hepatitis Antibodies / Q000032:analysis; D006509:Hepatitis B / Q000097:blood* / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000032:analysis / Q000276:immunology; D006526:Hepatitis C / Q000097:blood*; D006521:Hepatitis, Chronic / Q000097:blood*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration
D004338:Drug Combinations; D006508:Hepatitis Antibodies; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D015088:2',5'-Oligoadenylate Synthetase; D007213:Indomethacin