In vitro effect of thymosin-alpha1 and interferon-alpha on Th1 and Th2 cytokine synthesis in patient

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Journal of Viral Hepatitis (OnlineEarly Articles).

doi:10.1111/j.1365-2893.2007.00960.x

Abstract

In vitro effect of thymosin-alpha1 and interferon-alpha on Th1 and Th2 cytokine

synthesis in patients with eAg-negative chronic hepatitis B

E. Loggi11Department of Internal Medicine, Cardioangiology and Hepatology, A.

Gramenzi11Department of Internal Medicine, Cardioangiology and Hepatology, M.

Margotti11Department of Internal Medicine, Cardioangiology and Hepatology, C.

Cursaro11Department of Internal Medicine, Cardioangiology and Hepatology, S.

Galli22Microbiology Section, Department of Clinical and Experimental Medicine,

University of Bologna, Bologna, Italy, G. Vitale11Department of Internal

Medicine, Cardioangiology and Hepatology, E. Grandini11Department of Internal

Medicine, Cardioangiology and Hepatology, A. Scuteri11Department of Internal

Medicine, Cardioangiology and Hepatology, R. Vukotic11Department of Internal

Medicine, Cardioangiology and Hepatology, P. Andreone11Department of Internal

Medicine, Cardioangiology and Hepatology and M. Bernardi11Department of Internal

Medicine, Cardioangiology and Hepatology1Department of Internal Medicine,

Cardioangiology and Hepatology and 2Microbiology Section, Department of Clinical

and Experimental Medicine, University of Bologna, Bologna, Italy

Pietro Andreone MD, Servizio di Semeiotica Medica, Department of Internal

Medicine, Cardioangiology and Hepatology, University of Bologna, Via Massarenti,

9, Bologna, Italy. E-mail: andreone@...

Abstract

Summary. Thymosin alpha-1 (Tá1) has been shown to be effective in chronic

hepatitis B treatment. This study investigated the effect of Tá1 and

interferon-alpha (IFNá) 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 Tá1, IFNá or both on the synthesis of

T-helper 1 (Th1) cytokines [interleukin-2 (IL-2), IFNã] 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, IFNá/Tá1

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, IFNá increased the synthesis of IL-10 compared with baseline.

Interestingly, both Tá1 alone and the IFNá/Tá1 combination reversed this effect.

Finally, compared with baseline, the synthesis of 2',5'-OAS was significantly

higher in the presence of Tá1 and IFNá alone, and in the presence of IFNá/Tá1

association, while no differences were found between controls and HBV patients.

In conclusion, in PBMCs from eAg-negative HBV patients, Tá1 alone was able to

increase the antiviral protein synthesis, while in association with IFNá, 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.

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