| Silymarin inhibits in vitro T-cell proliferation and cytokine production in hepatitis C virus infection. | |
| | |
MedLine Citation:
|
PMID: 19782083 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND & 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 United States, its clinical efficacy remains uncertain. The goal of this study was to determine whether silymarin has in vitro effects on immune function that might have implications for its potential effect on hepatitis C virus (HCV)-induced liver disease. METHODS: Freshly isolated peripheral blood mononuclear cells (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 and 40 microg/mL. MK001 dose dependently inhibited the proliferation and secretion of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (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/HCV 1406-1415-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 nuclear factor-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. CONCLUSIONS: Silymarin's ability to inhibit the proliferation and proinflammatory cytokine secretion of T cells, combined with its previously described antiviral effect, suggests a possible mechanism of action that could lead to clinical benefit during HCV infection. |
| | |
Authors:
|
Chihiro Morishima; Margaret C Shuhart; Chia C Wang; Denise M Paschal; Minjun C Apodaca; Yanze Liu; Derek D Sloan; Tyler N Graf; Nicholas H Oberlies; David Y-W Lee; Keith R Jerome; Stephen J Polyak |
Related Documents
:
|
1979333 - Basis for defective proliferation of peripheral blood t cells to anti-cd2 antibodies in... 8393043 - Anti-cytokine antibodies as carrier proteins. prolongation of in vivo effects of exogen... 19118173 - Cytoplasmic inclusions of htt exon1 containing an expanded polyglutamine tract suppress... |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural Date: 2009-09-24 |
Journal Detail:
|
Title: Gastroenterology Volume: 138 ISSN: 1528-0012 ISO Abbreviation: Gastroenterology Publication Date: 2010 Feb |
Date Detail:
|
Created Date: 2010-02-09 Completed Date: 2010-04-01 Revised Date: 2011-09-26 |
Medline Journal Info:
|
Nlm Unique ID: 0374630 Medline TA: Gastroenterology Country: United States |
Other Details:
|
Languages: eng Pagination: 671-81, 681.e1-2 Citation Subset: AIM; IM |
Affiliation:
|
Division of Virology, Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington 98104, USA. chihiro@u.washington.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Antioxidants
/
pharmacology Case-Control Studies Cell Line Cell Proliferation / drug effects* Cells, Cultured Cytokines / metabolism* Dose-Response Relationship, Drug Hepacivirus Hepatitis C / metabolism*, pathology* Humans Interferon-gamma / metabolism Interleukin-2 / metabolism Jurkat Cells Leukocytes, Mononuclear / drug effects, metabolism, pathology Silymarin / pharmacology* T-Lymphocytes / drug effects*, metabolism, pathology Tumor Necrosis Factor-alpha / metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
R01 CA104286/CA/NCI NIH HHS; R01 CA104286-05/CA/NCI NIH HHS; R21 AT002895/AT/NCCAM NIH HHS; R21 AT002895-01A2/AT/NCCAM NIH HHS; R21 AT002895-02/AT/NCCAM NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antioxidants; 0/Cytokines; 0/Interleukin-2; 0/Silymarin; 0/Tumor Necrosis Factor-alpha; 82115-62-6/Interferon-gamma |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A functional role for CCR6 on proallergic T cells in the gastrointestinal tract.
Next Document: Serum levels of interleukin-10 and interleukin-12 predict early, spontaneous hepatitis B virus e ant...