Silymarin suppresses basal and stimulus-induced activation, exhaustion, differentiation, and inflammatory markers in primary human immune cells.
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.
Department of Laboratory Medicine, University of Washington, Seattle, WA, United States of America.
Erica S
ES
Lovelace
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
Nicholas J
NJ
Maurice
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
Hannah W
HW
Miller
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.|Department of Global Health, University of Washington, Seattle, WA, United States of America.
Chloe K
CK
Slichter
Division of Allergy and Infectious Disease, University of Washington, Seattle, WA, United States of America.
Robert
R
Harrington
Department of Laboratory Medicine, University of Washington, Seattle, WA, United States of America.|Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.|Department of Biostatistics, University of Washington, Seattle, WA, United States of America.
Amalia
A
Magaret
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.|Department of Global Health, University of Washington, Seattle, WA, United States of America.
Martin
M
Prlic
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
Stephen
S
De Rosa
Department of Laboratory Medicine, University of Washington, Seattle, WA, United States of America.|Department of Global Health, University of Washington, Seattle, WA, United States of America.|Department of Microbiology, University of Washington, Seattle, WA, United States of America.
Stephen J
SJ
Polyak
D015415:Biomarkers / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D000072336:Mucosal-Associated Invariant T Cells / Q000187:drug effects / Q000378:metabolism; D000069452:Pathogen-Associated Molecular Pattern Molecules / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012838:Silymarin / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism*
D015415:Biomarkers; D000069452:Pathogen-Associated Molecular Pattern Molecules; D011948:Receptors, Antigen, T-Cell; D012838:Silymarin