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

Abstract

Current evidences suggest that non-steroidal anti-inflammatory drugs could enhance the antiviral activity of interferon-\u3b1 in chronic HCV infection. In this study, we investigated the effect of indomethacin, a non-steroidal anti-inflammatory drug, and interferon-\u3b1 on cytokine production by peripheral blood mononuclear cells from 12 untreated patients with chronic hepatitis C. We evaluated the effect of incubation with indomethacin, interferon-\u3b1 or both on synthesis of Th1- (interleukin-2, interferon-\u3b3) and Th2-associated cytokines (interleukin-4, interleukin-10), and of the antiviral protein 2\u2032,5\u2032-oligoadenylate synthetase. Interferon-\u3b1 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-\u3b1 leads to a synergistic effect. Incubation with indomethacin decreased both interleukin-4 and interleukin-10, whereas interferon-\u3b1 increased these cytokines. The addition of indomethacin to interferon-\u3b1 significantly reversed this interferon-induced increase. Finally, both indomethacin and the association interferon-\u3b1 plus indomethacin determined a significant increase in 2\u2032,5\u2032-oligoadenylate synthetase production compared to both baseline and interferon-\u3b1 alone. In conclusion, indomethacin was able to enhance the antiviral activity of interferon-\u3b1 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 persistenc