Bile acid inhibition of interferon activity in human lymphocytes: no evidence of oxidative stress.
Cholestasis and bile acids are two factors involved in resistance to interferon therapy in patients with chronic hepatitis C. As bile acids inhibit the biological activity of this cytokine in vitro and are capable of generating oxidative stress in hepatocytes, we investigated the potential involvement of such a mechanism in human lymphocytes. Thus, we evaluated (a) the effects of bile acids (0-200 mumol L-1) on lymphocyte reduced glutathione content and malondialdehyde production and (b) the ability of antioxidants to prevent the inhibitory effect of chenodeoxycholic acid on interferon-induced lymphocyte 2',5'-oligoadenylate synthetase activity, an index of the biological activity of interferon. We found that treatment of lymphocytes with bile acids for 24 h did not induce malondialdehyde release or significantly modify cellular reduced glutathione content. Synthetic precursors of glutathione (N-acetylcysteine and S-adenosylmethionine) and antioxidants (superoxide dismutase and catalase) had no preventive influence on the inhibitory effect of chenodeoxycholic acid on interferon-induced 2',5'-oligoadenylate synthetase activity. These negative results do not provide evidence for the use of glutathione precursors in cholestatic conditions associated with viral diseases.
Podevin
P
P
Service d'Hépatologie, Hôpital Saint-Antoine, Paris, France.
Blanc
M C
MC
Vaubourdolle
M
M
Veyrunes
C
C
Bonnefis
M T
MT
Poupon
R
R
D015088:2',5'-Oligoadenylate Synthetase / Q000037:antagonists & inhibitors; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D002779:Cholestasis / Q000150:complications / Q000378:metabolism / Q000628:therapy; D004351:Drug Resistance; D005978:Glutathione / Q000378:metabolism; D006526:Hepatitis C / Q000150:complications / Q000378:metabolism / Q000628:therapy; D006801:Humans; D066298:In Vitro Techniques; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D011994:Recombinant Proteins
D001647:Bile Acids and Salts; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002635:Chenodeoxycholic Acid; D008315:Malondialdehyde; D015088:2',5'-Oligoadenylate Synthetase; D005978:Glutathione