Silymarin Inhibits in Vitro T Cell Proliferation and Cytokine Production in Hepatitis C Virus Infection

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Tyler Graf, Research Scientist (Creator)
Nicholas Oberlies, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: Background and Aims: Silymarin, an extract from the seeds of the milk thistle plant Silybum marianum, has been used for centuries for the treatment of chronic liver diseases. Despite common use by patients with hepatitis C in the U.S., its clinical efficacy remains uncertain. The goal of this study was to determine if silymarin has in vitro effects on immune function that might have implications for its potential effect on HCV-induced liver disease.

Methods: Freshly isolated PBMC and T cells from HCV-infected and uninfected subjects were tested in vitro for responses to nonspecific and antigenic stimulation in the presence and absence of a standardized preparation of silymarin (MK001).

Results: Minimal MK001 toxicity on PBMC was found at concentrations between 5-40 µg/mL. MK001 dose-dependently inhibited the proliferation and secretion of TNF-a, IFN-?, and IL-2 by PBMC stimulated with anti-CD3. In addition, MK001 inhibited proliferation by CD4+ T cells to HCV, Candida and Tetanus protein antigens, and by HLA-A2/HCV1406-1415-specific CD8+ T cells to allogeneic stimulation. MK001 inhibited T cell TNF-a and IFN-? cytokine secretion to Tetanus and Candida protein antigens. Finally, MK001 inhibited NF-?B transcriptional activation after T cell receptor-mediated stimulation of Jurkat T cells, consistent with its ability to inhibit Jurkat T cell proliferation and secretion of IL-2.

Conclusion: Silymarin’s ability to inhibit the proliferation and pro-inflammatory cytokine secretion of T cells, combined with its previously described anti-viral effect suggests a possible mechanism of action that could lead to clinical benefit during HCV infection.

Additional Information

Publication
Gastroenterology, 138 (2), 671-681.
Language: English
Date: 2010
Keywords
Milk thistle, Silybum marianum, Silymarin, Silibinin, Immune, T cell, Hepatitis C, HCV, Anti-inflammatory, Proliferation, Cytokine

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