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

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.
AuthorsE Loggi, A Gramenzi, M Margotti, C Cursaro, S Galli, G Vitale, E Grandini, A Scuteri, R Vukotic, P Andreone, M Bernardi
JournalJournal of viral hepatitis (J Viral Hepat) Vol. 15 Issue 6 Pg. 442-8 (Jun 2008) ISSN: 1365-2893 [Electronic] England
PMID18221304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiviral Agents
  • Hepatitis B e Antigens
  • Interferon-alpha
  • Interleukin-2
  • thymalfasin
  • Interleukin-4
  • Thymosin
  • 2',5'-Oligoadenylate Synthetase
  • 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)
  • Thymosin (analogs & derivatives, pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: