Abstract
d-Limonene, a cyclic terpene that is a major component of several plant essential oils, is used widely as an additive in perfumes, soaps, foods and beverages, and has also been shown to possess chemopreventative and chemotherapeutic activity. A limited number of studies have been conducted investigating the effect of d-limonene on immune system function. We show that d-limonene and its metabolites limonene-1-2-diol and perillic acid inhibit the production by CD3(+)CD4(+) T cells of IFN-γ, IL-2, TNF-α, IL-4 and IL-13, and the production by CD3(+)CD8(+) T cells of IFN-γ, IL-2, and TNF-α. Additionally, the upregulation of CD25, CD69 and CD40L by activated T lymphocytes is modulated by d-limonene, limonene-1-2-diol and perillic acid treatment. Furthermore, high concentrations of d-limonene, limonene-1-2-diol and perillic acid induce T lymphocyte cell death. These data suggest that d-limonene possesses immunomodulatory activity that must be considered when utilizing the compound for therapeutic or commercial purposes.
Copyright © 2012 Elsevier Inc. All rights reserved.
MeSH terms
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Animals
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Anticarcinogenic Agents / pharmacology
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Antigens, CD / immunology
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Antigens, CD / metabolism
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Antigens, Differentiation, T-Lymphocyte / immunology
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Antigens, Differentiation, T-Lymphocyte / metabolism
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CD3 Complex / immunology
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CD3 Complex / metabolism
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CD4-Positive T-Lymphocytes / drug effects*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD40 Ligand / immunology
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CD40 Ligand / metabolism
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CD8-Positive T-Lymphocytes / drug effects*
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cell Survival / immunology
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Cells, Cultured
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Cyclohexenes / metabolism
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Cyclohexenes / pharmacology*
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Dose-Response Relationship, Drug
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Enzyme-Linked Immunosorbent Assay
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Female
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Flow Cytometry
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Interleukin-13 / immunology
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Interleukin-13 / metabolism
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Interleukin-2 / immunology
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Interleukin-2 / metabolism
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Interleukin-2 Receptor alpha Subunit / immunology
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Interleukin-2 Receptor alpha Subunit / metabolism
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Interleukin-4 / immunology
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Interleukin-4 / metabolism
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Lectins, C-Type / immunology
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Lectins, C-Type / metabolism
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Limonene
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Mice
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Mice, Inbred C57BL
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Monoterpenes / pharmacology
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Terpenes / metabolism
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Terpenes / pharmacology*
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Anticarcinogenic Agents
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD3 Complex
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CD69 antigen
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Cyclohexenes
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Interleukin-13
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Interleukin-2
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Interleukin-2 Receptor alpha Subunit
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Lectins, C-Type
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Monoterpenes
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Terpenes
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Tumor Necrosis Factor-alpha
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CD40 Ligand
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Interleukin-4
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perillic acid
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Interferon-gamma
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Limonene