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 (T alpha 1) has been shown to be effective in chronic hepatitis B treatment. This study investigated the effect of T alpha 1 and interferon-alpha (IFN alpha) 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 T alpha 1, IFN alpha or both on the synthesis of T-helper 1 (Th1) cytokines [interleukin-2 (IL-2), IFN gamma] 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, IFN alpha/T alpha 1 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, IFN alpha increased the synthesis of IL-10 compared with baseline. Interestingly, both T alpha 1 alone and the IFN alpha/T alpha 1 combination reversed this effect. Finally, compared with baseline, the synthesis of 2',5'-OAS was significantly higher in the presence of T alpha 1 and IFN alpha alone, and in the presence of IFN alpha/T alpha 1 association, while no differences were found between controls and HBV patients. In conclusion, in PBMCs from eAg-negative HBV patients, T alpha 1 alone was able to increase the antiviral protein synthesis, while in association with IFN alpha, 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.