In vitro effect of thymosin-alpha1 and interferon-alpha on Th1 and Th2 cytokine synthesis in patients with eAg-negative chronic hepatitis B.

Abstract

Thymosin alpha-1 (Talpha1) has been shown to be effective in chronic hepatitis B treatment. This study investigated the effect of Talpha1 and interferon-alpha (IFNalpha) on cytokine production by peripheral blood mononuclear cells (PBMCs) of 12 patients with eAg-negative chronic hepatitis B (HBV). We evaluated the effect of incubation with Talpha1, IFNalpha or both on the synthesis of T-helper 1 (Th1) cytokines [interleukin-2 (IL-2), IFNgamma] and Th2 cytokines (IL-4, IL-10) and of antiviral protein 2',5'-oligoadenylate synthetase (2',5'-OAS) in patients and in a group of 10 healthy controls. Concerning Th1 profile, controls showed lower IL-2 synthesis than HBV patients. In HBV setting, IFNalpha/Talpha1 combination was able to increase IL-2 production significantly, when compared with baseline condition. About the Th2-cytokines, controls showed statistically lower synthesis of IL-4 and higher production of IL-10, than HBV patients. In these latter, IFNalpha increased the synthesis of IL-10 compared with baseline. Interestingly, both Talpha1 alone and the IFNalpha/Talpha1 combination reversed this effect. Finally, compared with baseline, the synthesis of 2',5'-OAS was significantly higher in the presence of Talpha1 and IFNalpha alone, and in the presence of IFNalpha/Talpha1 association, while no differences were found between controls and HBV patients. In conclusion, in PBMCs from eAg-negative HBV patients, Talpha1 alone was able to increase the antiviral protein synthesis, while in association with IFNalpha, it stimulated the IL-2 synthesis and inhibited the IFN-induced IL-10 production. These results need further investigations, but reinforce the idea of an immunotherapeutic approach for chronic hepatitis B.

• Authors: E Loggi, A Gramenzi, M Margotti, C Cursaro, S Galli, G Vitale, E Grandini, A Scuteri, R Vukotic, P Andreone, M Bernardi
• Journal: Journal of viral hepatitis (J Viral Hepat) Vol. 15 Issue 6 Pg. 442-8 (Jun 2008) ISSN: 1365-2893 [Electronic] England
• PMID: 18221304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Hepatitis B e Antigens
• Interferon-alpha
• Interleukin-2
• Interleukin-4
• Thymosin
• 2',5'-Oligoadenylate Synthetase
• Thymalfasin

Topics

• 2',5'-Oligoadenylate Synthetase (biosynthesis)
• Adult
• Antiviral Agents (pharmacology)
• Cells, Cultured
• Female
• Hepatitis B e Antigens (blood)
• Hepatitis B, Chronic (immunology, metabolism)
• Humans
• Interferon-alpha (pharmacology)
• Interleukin-2 (biosynthesis)
• Interleukin-4 (biosynthesis)
• Leukocytes, Mononuclear (drug effects, metabolism)
• Male
• Middle Aged
• Th1 Cells (drug effects, metabolism)
• Th2 Cells (drug effects, metabolism)
• Thymalfasin
• Thymosin (analogs & derivatives, pharmacology)