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.