Cited by 172Cannabis and Cannabinoid ResearchImmunotoxicology and immune responsesInflammatory mediators and NSAID effects

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Cannabinoid-Induced Immune Suppression and Modulation of Antigen-Presenting Cells

Klein, Thomas W., Cabral, Guy A.·2006·Journal of Neuroimmune Pharmacology

DOI 10.1007/s11481-005-9007-x

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Abstract

The study of marijuana cannabinoid biology has led to many important discoveries in neuroscience and immunology. These studies have uncovered a new physiological system, the endocannabinoid system, which operates in the regulation of not only brain function but also the regulation of the immune system. Studies examining the effect of cannabinoid-based drugs on immunity have shown that many cellular and cytokine mechanisms are suppressed by these agents leading to the hypothesis that these drugs may be of value in the management of chronic inflammatory diseases. In this report, we review current information on cannabinoid ligand and receptor biology, mechanisms involved in immune suppression by cannabinoids with emphasis on antigen-presenting cells, and preclinical and clinical models analyzing the therapeutic potential of cannabinoid-based drugs.

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Cannabinoid Inhibition of Adenylate Cyclase-mediated Signal Transduction and Interleukin 2 (IL-2) Expression in the Murine T-cell Line, EL4.IL-2
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Simultaneous Measurement of Anandamide and 2-Arachidonoylglycerol by Polymyxin B-Selective Adsorption and Subsequent High-Performance Liquid Chromatography Analysis: Increase in Endogenous Cannabinoids in the Sera of Patients with Endotoxic Shock
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2-Arachidonoylglycerol Induces the Migration of HL-60 Cells Differentiated into Macrophage-like Cells and Human Peripheral Blood Monocytes through the Cannabinoid CB2 Receptor-dependent Mechanism
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In vivo and in vitro treatment with the synthetic cannabinoid CP55,940 decreases the in vitro migration of macrophages in the rat: involvement of both CB1 and CB2 receptors
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Cannabinoid Inhibition of the Processing of Intact Lysozyme by Macrophages: Evidence for CB2 Receptor Participation
McCoy, K. L., Matveyeva, M., Carlisle, S. J., & Cabral, G. A. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38313-2 · Cited by 116
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Suppression of experimetal autoimmune encephalomyelitis by cannabinoids
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Cannabinoids and Multiple Sclerosis
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Cardiovascular actions of cannabinoids and their generation during shock
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Effects on the Immune System
Cabral, G. A., & Staab, A. (2005) · Handbook of experimental pharmacology · doi:10.1007/3-540-26573-2_13 · Cited by 108
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The endogenous cannabinoid anandamide potentiates interleukin‐6 production by astrocytes infected with Theiler's murine encephalomyelitis virus by a receptor‐mediated pathway
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Anandamide, a Natural Ligand for the Peripheral Cannabinoid Receptor Is a Novel Synergistic Growth Factor for Hematopoietic Cells
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The Effect of Delta-9-Tetrahydrocannabinol and 11-Hydroxy-Delta-9-Tetrahydrocannabinol on T-Lymphocyte and B-Lymphocyte Mitogen Responses
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“THC was noted (Klein et al. 1985) to suppress mouse splenocyte T-lymphocyte proliferation in response to the T-cell mitogens ConA and PHA as well as that of B lymphocytes induced by bacterial lipopolysaccharide (LPS), a B-cell mitogen.”
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Drugs of abuse and immune function
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Synthetic nonpsychotropic cannabinoids with potent antiinflammatory, analgesic, and leukocyte antiadhesion activities
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Dimethylheptyl-THC-11 OIC acid: A nonpsychoactive antiinflammatory agent with a cannabinoid template structure
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Marijuana components suppress induction and cytolytic function of murine cytotoxic T cells in vitro and in vivo
Klein, T., Kawakami, Y., Newton, C. A., & Friedman, H. P. (1991) · Journal of Toxicology and Environmental Health · doi:10.1080/15287399109531496 · Cited by 94
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2-Arachidonoylglycerol, an Endogenous Cannabinoid Receptor Ligand, Induces Accelerated Production of Chemokines in HL-60 Cells
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Evidence for Cannabinoid Receptor-Dependent and -Independent Mechanisms of Action in Leukocytes
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Ajulemic acid: A novel cannabinoid produces analgesia without a “high”
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Tetrahydrocannabinol inhibition of macrophage nitric oxide production
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The endocannabinoid signaling system: Pharmacological and therapeutic aspects
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delta 9-Tetrahydrocannabinol modulates antigen processing by macrophages.
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“This suggested that specific proteases, whose function is requisite for processing of specific antigens, were affected by THC (McCoy et al. 1995).”
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In vitro and in vivo suppressive effects of delta-9-tetrahydrocannabinol on interferon production by murine spleen cells
Blanchard, D. K., Newton, C. A., Klein, T., Stewart, W. E., & Friedman, H. P. (1986) · International Journal of Immunopharmacology · doi:10.1016/0192-0561(86)90020-2 · Cited by 69
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Anandamide inhibits macrophage-mediated killing of tumor necrosis factor-sensitive cells
Cabral, G. A., TONEY, D. M., Fischer‐Stenger, K., Harrison, M. P., & Marciano‐Cabral, F. (1995) · Life Sciences · doi:10.1016/0024-3205(95)00190-h · Cited by 69
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Protection Against Septic Shock and Suppression of Tumor Necrosis Factor α and Nitric Oxide Production by Dexanabinol (HU-211), a Nonpsychotropic Cannabinoid
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Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production by dexanabinol (HU-211), a nonpsychotropic cannabinoid.
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2-arachidonyl-glycerol stimulates nitric oxide release from human immune and vascular tissues and invertebrate immunocytes by cannabinoid receptor 1
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Suppression of human monocyte interleukin-1β production by ajulemic acid, a nonpsychoactive cannabinoid
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9-Tetrahydrocannabinol Decreases Alpha/Beta Interferon Response to Herpes Simplex Virus Type 2 in the B6C3F1 Mouse
Cabral, G. A., Lockmuller, J. C., & Mishkin, E. M. (1986) · Experimental Biology and Medicine · doi:10.3181/00379727-181-42258 · Cited by 59
Self-citation
Delta-9-Tetrahydrocannabinol Decreases Host Resistance to Herpes Simplex Virus Type 2 Vaginal Infection in the B6C3F1 Mouse
Mishkin, E. M., & Cabral, G. A. (1985) · Journal of General Virology · doi:10.1099/0022-1317-66-12-2539 · Cited by 57
Self-citation
1',1'-Dimethylheptyl-delta-8-tetrahydrocannabinol-11-oic acid: a novel, orally effective cannabinoid with analgesic and anti-inflammatory properties.
Dajani, E. Z., Larsen, K. R., Taylor, J., Dajani, N. E., Shahwan, T. G., Neeleman, S. D., Taylor, M., Dayton, M. T., & Mir, G. (1999) · PubMed · Cited by 57
Distinct Expression Profiles of the Peripheral Cannabinoid Receptor in Lymphoid Tissues Depending on Receptor Activation Status
Rayman, N., Lam, K. H., Laman, J. D., Simons, P. J., Löwenberg, B., Sonneveld, P., & Delwel, R. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.4.2111 · Cited by 49
Role of cannabinoid receptors in inhibiting macrophage costimulatory activity
Chuchawankul, S., Shima, M., Buckley, N. E., Hartmann, C. B., & McCoy, K. L. (2004) · International Immunopharmacology · doi:10.1016/j.intimp.2003.12.011 · Cited by 48
Differential Inhibition of RAW264.7 Macrophage Tumoricidal Activity by 9Tetrahydrocannabinol
Burnette-Curley, D., & Cabral, G. A. (1995) · Experimental Biology and Medicine · doi:10.3181/00379727-210-43926 · Cited by 48
Self-citation
Cannabinoid-mediated exacerbation of brain infection by opportunistic amebae
Cabral, G. A., & Marciano‐Cabral, F. (2003) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2003.10.027 · Cited by 45
Self-citation
Delta-9-tetrahydrocannabinol inhibits cell contact-dependent cytotoxicity of bacillus calmétte-guérin-activated macrophages
Burnette-Curley, D., Marciano‐Cabral, F., Fischer‐Stenger, K., & Cabral, G. A. (1993) · International Journal of Immunopharmacology · doi:10.1016/0192-0561(93)90048-4 · Cited by 41
Self-citation
Influence of Marijuana Components (THC and CBD) on Human Mononuclear Cell Cytokine Secretion In vitro
Watzl, B., Scuderi, P., & WATSON, R. R. (1991) · Advances in experimental medicine and biology · doi:10.1007/978-1-4684-5925-8_7 · Cited by 39
Vasorelaxant activities of the putative endocannabinoid virodhamine in rat isolated small mesenteric artery
Ho, W. ‐. V., & Hiley, C. R. (2004) · Journal of Pharmacy and Pharmacology · doi:10.1211/0022357023682 · Cited by 38
Induction of Interleukin-2 Receptor α Gene by Δ 9 -Tetrahydrocannabinol Is Mediated by Nuclear Factor κB and CB1 Cannabinoid Receptor
Daaka, Y., Zhu, W., Friedman, H., & Klein, T. (1997) · DNA and Cell Biology · doi:10.1089/dna.1997.16.301 · Cited by 38
Self-citation
9-Tetrahydrocannabinol Decreases Cytotoxic T Lymphocyte Activity to Herpes Simplex Virus Type 1-Infected Cells
Fischer‐Stenger, K., Updegrove, A. W., & Cabral, G. A. (1992) · Experimental Biology and Medicine · doi:10.3181/00379727-200-43452 · Cited by 36
Self-citation
Delta‐9‐tetrahydrocannabinol inhibits macrophage protein expression in response to bacterial immunomodulators
Cabral, G. A., & Mishkin, E. M. (1989) · Journal of Toxicology and Environmental Health · doi:10.1080/15287398909531243 · Cited by 34
Self-citation
9-Tetrahydrocannabinol Suppresses Macrophage Extrinsic Antiherpesvirus Activity
Cabral, G. A., & Vasquez, R. (1992) · Experimental Biology and Medicine · doi:10.3181/00379727-199-43356 · Cited by 34
Self-citation
Effect of the cannabinoid ajulemic acid on rat models of neuropathic and inflammatory pain
Mitchell, V. A., Aslan, S. C., Safaei, R., & Vaughan, C. W. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.03.019 · Cited by 31
Suppression by Cannabinoids of a Cloned Cell Line with Natural Killer Cell Activity
Kawakami, Y., Klein, T., Newton, C., Djeu, J. Y., Dennert, G., Specter, S., & Friedman, H. (1988) · Experimental Biology and Medicine · doi:10.3181/00379727-187-42676 · Cited by 29
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Δ9-tetrahydrocannabinol suppresses concanavalin a induced increase in cytoplasmic free calcium in mouse thymocytes
Yebra, M., Klein, T., & Friedman, H. (1992) · Life Sciences · doi:10.1016/0024-3205(92)90009-e · Cited by 27
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1′,1′-Dimethylheptyl-Δ-8-tetrahydrocannabinol-11-oic Acid: A Novel, Orally Effective Cannabinoid with Analgesic and Anti-inflammatory Properties
Dajani, E. Z., Larsen, K. R., Taylor, J., Dajani, N. E., Shahwan, T. G., Neeleman, S. D., Taylor, M. S., Dayton, M. T., & Mir, G. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35067-0 · Cited by 25
Modulation of Interleukin 2 Activity by 9-Tetrahydrocannabinol after Stimulation with Concanavalin A, Phytohemagglutinin, or Anti-CD3 Antibody
Nakano, Y., Pross, S. H., & Friedman, H. P. (1992) · Experimental Biology and Medicine · doi:10.3181/00379727-201-43494c · Cited by 24
Resistance to Legionella pneumophila Suppressed by the Marijuana Component, Tetrahydrocannabinol
Klein, T., Newton, C. A., & Friedman, H. P. (1994) · The Journal of Infectious Diseases · doi:10.1093/infdis/169.5.1177-a · Cited by 23
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Immunosuppression by Marijuana and Components
Friedman, H. P., Klein, T., & Specter, S. C. (1991) · Elsevier eBooks · doi:10.1016/b978-0-12-043780-1.50041-5 · Cited by 22
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delta 9-Tetrahydrocannabinol (THC) causes the variable expression of IL2 receptor subunits.
Zhu, W., Igarashi, T., Friedman, H. P., & Klein, T. (1995) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)10542-9 · Cited by 15
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Zurier, R. B., Rossetti, R. G., Lane, J. H., Goldberg, J. M., Hunter, S. A., & BURSTEIN, S. H. (1999) · Humana Press eBooks · doi:10.1007/978-1-59259-710-9_49 · Cited by 8

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Authors: Klein, T. W., & Cabral, G. A.
Affiliations: University of South Florida (US)
Virginia Commonwealth University (US)
Corresponding author: Klein, Thomas W.
ORCID: Klein, Thomas W.
Venue: Journal of Neuroimmune Pharmacology
Publisher: Springer Science and Business Media LLC
Published: 2006-02-22
Volume: 1
Issue: 1
Pages: 50-64
ISSN: 1557-1890 (ISSN-L)
1557-1904
DOI: 10.1007/s11481-005-9007-x
OpenAlex: W2061663043
Cited by: 172
References: 139
Citations by year: 2026: 4 · 2025: 6 · 2024: 8 · 2023: 6 · 2022: 4 · 2021: 12 · 2020: 16 · 2019: 9 · 2018: 6 · 2017: 11 · 2016: 13 · 2015: 6 · 2014: 9 · 2013: 13 · 2012: 6
FWCI: 0.94
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Journal of Neuroimmune Pharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Drug Abuse (DA15608, DA05832, R01DA003646, DA03646, R01DA015608)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
Keywords: cannabinoids, endocannabinoid system, immunosuppression, antigen-presenting cells, cannabinoid receptors, cytokines, chronic inflammatory diseases, immunomodulation
MeSH terms: Animals, Antigen-Presenting Cells, Cannabinoids, Cannabis, Humans, Inflammation, Receptors, Cannabinoid

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Cannabinoid-Induced Immune Suppression and Modulation of Antigen-Presenting Cells

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