Silymarin Inhibits in Vitro T Cell Proliferation and Cytokine Production in Hepatitis C Virus Infection. Gastroenterology [Gastroenterology] Journal article

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 mug/mL. MK001 dose-dependently inhibited the proliferation and secretion of TNF-alpha, IFN-gamma, 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-alpha and IFN-gamma cytokine secretion to Tetanus and Candida protein antigens. Finally, MK001 inhibited NF-kappaB 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.

Gastroenterology [Gastroenterology]