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.
Loggi
E
E
Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Bologna, Italy.
Gramenzi
A
A
Margotti
M
M
Cursaro
C
C
Galli
S
S
Vitale
G
G
Grandini
E
E
Scuteri
A
A
Vukotic
R
R
Andreone
P
P
Bernardi
M
M
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis*; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D007376:Interleukin-2; D015847:Interleukin-4; D013947:Thymosin; D015088:2',5'-Oligoadenylate Synthetase; D000077596:Thymalfasin