In vitro effect of thymosin-alpha1 and interferon-alpha on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C.
Current evidence suggests that increased expression of Th1-associated cytokines is important for immune-mediated eradication of hepatitis C infection, while an increase in Th2-associated cytokines is associated with persistence of infection. In this study we evaluated the effects of thymosin-alpha1 (TA1), a naturally occurring thymic peptide, and interferon-alpha (IFN-alpha) on cytokine production in peripheral blood mononuclear cells from untreated patients with chronic hepatitis C. We examined the effect of incubation with TA1, IFN-alpha, or both, on production of Th1-associated cytokines (IL-2, IFN-gamma), Th2-associated cytokines (IL-4, IL-10), and synthesis of the antiviral protein 2',5'-oligoadenylate synthetase. TA1 treatment induced a significant increase in production of IL-2 and 2',5'-oligoadenylate synthetase. Smaller increases were also seen after treatment with IFN-alpha, while incubation with TA1 and IFN-alpha together led to an additive or synergistic effect. Incubation with TA1 resulted in a decrease in IL-4 and IL-10, whereas IFN-alpha increased these cytokines. The addition of TA1 to IFN-alpha significantly reversed this IFN-alpha-induced increase. Hence, TA1 treatment could benefit patients with hepatitis C infection by increasing the Th1-type response, fundamental for sustained clearance of hepatitis C; and by decreasing the Th2-type response, associated with persistence of viraemia.
Andreone
P
P
Semeiotica Medica, Dipartimento di Medicina Interna, Cardioangiologia ed Epatologia, Università di Bologna, Policlinico S. Orsola, Via Massarenti, 9-40138 Bologna, Italy. andreone@med.unibo.it
Cursaro
C
C
Gramenzi
A
A
Margotti
M
M
Ferri
E
E
Talarico
S
S
Biselli
M
M
Felline
F
F
Tuthill
C
C
Martins
E
E
Gasbarrini
G
G
Bernardi
M
M
D015088:2',5'-Oligoadenylate Synthetase / Q000032:analysis / Q000096:biosynthesis / Q000097:blood; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D016207:Cytokines; D016898:Interferon-alpha; D003208:Concanavalin A; D013947:Thymosin; D015088:2',5'-Oligoadenylate Synthetase; D000077596:Thymalfasin