Silymarin suppresses basal and stimulus-induced activation, exhaustion, differentiation, and inflammatory markers in primary human immune cells

• Published in: PloS one Vol. 12; no. 2; p. e0171139
• Main Authors: Lovelace, Erica S., Maurice, Nicholas J., Miller, Hannah W., Slichter, Chloe K., Harrington, Robert, Magaret, Amalia, Prlic, Martin, De Rosa, Stephen, Polyak, Stephen J.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.02.2017; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; Biology and Life Sciences; Biomarkers - metabolism; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - metabolism; Cell activation; Cell lines; Cells, Cultured; Chronic infection; Cytokines; Exhaustion; Flow Cytometry; Hepatocytes; HIV; HIV infections; HIV Infections - immunology; Human immunodeficiency virus; Humans; Immune system; Immunological memory; Immunoregulation; Inflammation; Inflammation - metabolism; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Liver; Lymphocyte Activation - drug effects; Lymphocytes; Lymphocytes T; Markers; Medicine and Health Sciences; Metabolism; Milk thistle; Monocytes; Mucosa; Mucosal-Associated Invariant T Cells - drug effects; Mucosal-Associated Invariant T Cells - metabolism; Pathogen-Associated Molecular Pattern Molecules - metabolism; Receptors, Antigen, T-Cell - metabolism; Research and Analysis Methods; Silybum marianum; Silymarin; Silymarin - pharmacology; Stem cells; T cell receptors; T cells; T-cell receptor; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - metabolism; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0171139

Silymarin (SM), and its flavonolignan components, alter cellular metabolism and inhibit inflammatory status in human liver and T cell lines. In this study, we hypothesized that SM suppresses both acute and chronic immune activation (CIA), including in the context of HIV infection. SM treatment suppressed the expression of T cell activation and exhaustion markers on CD4+ and CD8+ T cells from chronically-infected, HIV-positive subjects. SM also showed a trend towards modifying CD4+ T cell memory subsets from HIV+ subjects. In the HIV-negative setting, SM treatment showed trends towards suppressing pro-inflammatory cytokines from non-activated and pathogen-associated molecular pattern (PAMP)-activated primary human monocytes, and non-activated and cytokine- and T cell receptor (TCR)-activated mucosal-associated invariant T (MAIT) cells. The data suggest that SM elicits broad anti-inflammatory and immunoregulatory activity in primary human immune cells. By using novel compounds to alter cellular inflammatory status, it may be possible to regulate inflammation in both non-disease and disease states.