In vitro effect of thymosin‐α1 and interferon‐α on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C

Abstract

Current evidence suggests that increased expression of Th1-associated cytokines is important for immune-mediated eradication of hepatitis C infection, while an increase in Th2-associated cytokines is associated with persistence of infection. In this study we evaluated the effects of thymosin-alpha1 (TA1), a naturally occurring thymic peptide, and interferon-alpha (IFN-alpha) on cytokine production in peripheral blood mononuclear cells from untreated patients with chronic hepatitis C. We examined the effect of incubation with TA1, IFN-alpha, or both, on production of Th1-associated cytokines (IL-2, IFN-gamma), Th2-associated cytokines (IL-4, IL-10), and synthesis of the antiviral protein 2',5'-oligoadenylate synthetase. TA1 treatment induced a significant increase in production of IL-2 and 2',5'-oligoadenylate synthetase. Smaller increases were also seen after treatment with IFN-alpha, while incubation with TA1 and IFN-alpha together led to an additive or synergistic effect. Incubation with TA1 resulted in a decrease in IL-4 and IL-10, whereas IFN-alpha increased these cytokines. The addition of TA1 to IFN-alpha significantly reversed this IFN-alpha-induced increase. Hence, TA1 treatment could benefit patients with hepatitis C infection by increasing the Th1-type response, fundamental for sustained clearance of hepatitis C; and by decreasing the Th2-type response, associated with persistence of viraemia.

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

“…Incubation of Ta1 in combination with IFNa was able to reverse the IFN-induced increase of IL-10. Finally, we confirmed that Ta1 amplifies the synthesis of IFN-induced antiviral protein 2,5-OAS [17].…”

“…The cells were resuspended at the concentration of 1 · 10 6 PBMC/mL and were then subjected to four different experimental conditions, all in the presence of Concanvalin A (ConA) at 10 mg/mL (Sigma); as previously reported [17,18], ConA was used as a polyclonal stimulus for triggering cytokine production.…”

Evaluation of the Immunomodulatory Properties of a Calf Lipid Thymus Extract and Standardization of a Method for Quantification of its Biological Activity

“…TP was also efficient in vivo in mice with experimental gut-derived sepsis. The significantly reduced mortality of the animals was followed by reduced production of IL-4 and increased production of IL-2 [17] .Similarly, thymosin 1 treatment induced a significant increase in production of IL-2 and a decrease in production of IL-4 and IL-10 by T cells from patients with chronic hepatitis C [31] . Our results showed that higher concentrations of Thymsol inhibited proliferation of spleen T cells in a dose dependent manner.…”

Immunomodulatory function of orally administered thymosin α1

“…It was used widely in clinical treatment of hepatitis B, hepatitis C, HIV and some tumors, such as melanoma, lung cancer, leukemia, squamous epithelial cancer, colon cancer, etc. (Kullavanuaya et al, 2001;Andreone et al, 2001;Garaci et al, 2000Saruc et al, 2003. There are two kinds of thymus products for clinical practice: One is Zadaxin.…”