In vitro effect of indomethacin and interferon-alpha on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C.
Current evidences suggest that non-steroidal anti-inflammatory drugs could enhance the antiviral activity of interferon-alpha 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 mononuclear cells from 12 untreated patients with chronic hepatitis C. We evaluated the effect of incubation with indomethacin, interferon-alpha or both on synthesis of Th1- (interleukin-2, interferon-gamma) and Th2-associated cytokines (interleukin-4, interleukin-10), and of the antiviral protein 2',5'-oligoadenylate synthetase. Interferon-alpha 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.
Andreone
Pietro
P
Semeiotica Medica, Dipartimento di Medicina Interna, Cardioangiologia ed Epatologia, Università di Bologna, Via Massarenti, 9, 40138 Bologna, Italy. andreone@med.unibo.it
Gramenzi
Annagiulia
A
Loggi
Elisabetta
E
Favarelli
Laura
L
Cursaro
Carmela
C
Margotti
Marzia
M
Biselli
Maurizio
M
Lorenzini
Stefania
S
Bernardi
Mauro
M
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000998:Antiviral Agents; D016207:Cytokines; D016898:Interferon-alpha; D007213:Indomethacin