title: Impact of oral silymarin on virus- and non-virus-specific T-cell responses in chronic hepatitis C infection.
abstract: Silymarin displays anti-inflammatory effects on T lymphocytes in vitro. The immunomodulatory properties of oral silymarin in vivo in humans with chronic hepatitis C have not previously been characterized. We hypothesized that silymarin would suppress T-cell proliferation and pro-inflammatory cytokine production of virus- and non-virus-specific T cells while increasing anti-inflammatory IL-10 production in vivo. Patients from one site of the SyNCH-HCV double-masked, placebo-controlled study of oral silymarin in prior interferon nonresponders with chronic hepatitis C provided blood samples at baseline and treatment week 20. Mononuclear cells were stimulated with recombinant HCV proteins and controls in (3) H-thymidine proliferation assays, IFNγ ELISPOT and IL-10 ELISPOT. The frequency of CD4(+) CD25(hi) and CD4(+) foxp3(+) regulatory T cells, serum cytokine levels, serum IP-10 and lymphocyte interferon-stimulated gene expression were also quantified at baseline and week 20. Thirty-two patients were recruited (10; placebo, 11; 420 mg three times a day, 11; 700 mg three times a day). Serum ALT and HCV RNA titres did not change in any group. HCV-specific CD4(+) T-cell proliferation and the frequency of IFNγ- and IL-10-producing T cells were not significantly changed in silymarin-treated subjects. However, C. albicans-induced T-cell IFNγ and phytohaemagglutinin-induced T-cell proliferation were suppressed by silymarin therapy. A trend towards augmentation of interferon-induced ISG15 expression was present in the high-dose silymarin group. While no effect on HCV-specific T cells was identified, these data confirm that high-dose oral silymarin exerts modest nonspecific immunomodulatory effects in vivo. The impact of this anti-inflammatory effect on long-term liver health in chronic hepatitis C merits future clinical investigation.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: O
authors.initials: O
authors.lastname: Adeyemo
authors.forename: H
authors.initials: H
authors.lastname: Doi
authors.forename: K
authors.initials: K
authors.lastname: Rajender Reddy
authors.forename: D E
authors.initials: DE
authors.lastname: Kaplan
mesh_terms: D000284:Administration, Oral; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D012838:Silymarin / Q000008:administration & dosage*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D010919:Placebos; D012838:Silymarin