In vitro effect of indomethacin and interferon-α on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C

Current evidences suggest that non-steroidal anti-inflaminatory drugs could enhance the antiviral activity of interferon-a in chronic HCV infection. In this study, we investigated the effect of indomethacin, a non-steroidal anti-inflammatory drug, and interferon-alpha on cytokine production by peripheral blood inononuclear cells from 12 untreated patients with chronic hepatitis C. We evaluated the effect of incubation with indomethacin, interferon-a or both on synthesis of Th I - (interleukin-2, interferon-gamma) and Th2-associated cytokines (interleukin-4, interieukin-10), and of the antiviral protein 2',5'-oligoadenylate synthetase. Interferon-a induced a significant increase in production of interleukin-2. Smaller increases were also seen in the presence of indomethacin, while incubation with both indomethacin and interferon-alpha leads to a synergistic effect. Incubation with indomethacin decreased both interleukin-4 and interleukin-10, whereas interferon-alpha increased these cytokines. The addition of indomethacin to interferon-alpha, significantly reversed this interferon-induced increase. Finally, both indomethacin and the association interferon-alpha plus indomethacin determined a significant increase in 2',5'-oligoadenylate synthetase production compared to both baseline and interferon-alpha alone. In conclusion, indomethacin was able to enhance the antiviral activity of interferon-alpha and to modulate the interferon-induced Th1 and Th2 cytokine response by increasing the Th1-response, fundamental for sustained clearance of HCV, and by decreasing the Th-2 type response, associated with HCV persistence. (C) 2003 Elsevier Ltd. All rights reserved.