The Effect of Delta-9-Tetrahydrocannabinol and 11-Hydroxy-Delta-9-Tetrahydrocannabinol on T-Lymphocyte and B-Lymphocyte Mitogen Responses
Abstract
Previous studies have shown that delta-9-tetrahydrocannabinol (THC) suppresses T-lymphocyte proliferation when added to human cell cultures. We report that THC when added to mouse splenocyte cultures suppressed T-lymphocyte (Con A, PHA) and B-lymphocyte (LPS) mitogen-induced proliferation. Although the ED50 concentrations (5 micrograms/ml; 1.6 X 10(-5)M) of THC were similar for suppressing all three mitogen responses, higher threshold concentrations of drug were required to effect suppression of the T-lymphocyte mitogen responses. Complete suppression of T- and B-lymphocyte responses was achieved with THC concentrations (8 micrograms/ml or 2.6 X 10(-5)M) which were not directly toxic as judged by vital dye exclusion. The hydroxylated metabolite of THC, 11-hydroxy-THC, was observed to be much less potent in the inhibition of lymphocyte proliferation. However, as with the parent compound, B-lymphocyte responses appeared to be the most affected by the drug. Additional studies demonstrated that both T- and B-lymphocyte proliferation is rapidly suppressed following THC treatment, not affected by a 24 hr. pretreatment with THC, and not as readily suppressed by THC in cultures containing 20% serum. Thus, THC appears to inhibit both T- and B-lymphocyte proliferation with B-lymphocyte responses displaying greater inhibition at lower drug concentration. The 11-hydroxy metabolite is much less suppressive in this system than the parent compound.
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Selective antagonists of both the CB2 receptor, SR144528, and CB1 receptor, rimonabant, reverse the suppression of IFN-γ and IL-12, indicating that these receptors play necessary roles in the modulation of proinflammatory cytokines.
“Selective antagonists of both the CB 2 receptor, SR144528, and CB 1 receptor, rimonabant, reverses the suppression of IFN-γ and IL-12, indicating that these receptors play necessary roles in the modulation of proinflammatory cytokines (Klein et al, 1985).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Klein et al, 1985
THC inhibits the proliferation of mouse splenic T cells stimulated by concanavalin A, and B cells stimulated by LPS.
“Similarly, THC inhibits the proliferation of mouse splenic T cells stimulated by concanavalin A, and B cells stimulated by LPS (Klein et al, 1985).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Klein et al, 1985
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Farahani, R. H. (2007) · Journal of Tissue Viability · doi:10.1016/j.jtv.2007.09.002 · Cited by 5 · see citing works
Pross, S. H., Newton, C. A., Klein, T., & Friedman, H. P. (1987) · Immunopharmacology · doi:10.1016/0162-3109(87)90014-2 · Cited by 5 · see citing works
Self-citationNakano, Y., Pross, S. H., Klein, T., & Friedman, H. P. (1993) · International Journal of Immunopharmacology · doi:10.1016/0192-0561(93)90054-3 · Cited by 5 · see citing works
Self-citationAge related immunomodulation in murine splenocytes induced by delta-9-tetrahydrocannabinol (THC)
Pross, S. H., Nakano, Y., Widen, R. E., McHugh, S. L., & Friedman, H. P. (1993) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(93)90136-f · Cited by 4 · see citing works
Self-citationImmunotoxicity and Inflammation: An Overview
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Delta-9-tetrahydrocannabinol: An inhibitor of STAT1α protein tyrosine phosphorylation
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Age-related suppression of murine lymphoid cell blastogenesis by marijuana components
Pross, S. H., Klein, T. W., Newton, C. A., Smith, J., Widen, R. E., & Friedman, H. (1990) · Developmental & Comparative Immunology · doi:10.1016/0145-305x(90)90015-7 · Cited by 2 · see citing works
Self-citationEisenstein, T. K., & Rogers, T. J. (2016) · Springer eBooks · doi:10.1007/978-3-319-44022-4_41 · Cited by 2 · see citing works
Suppression of T Lymphocyte Subpopulations by THC
Pross, S. H., Newton, C. A., Klein, T., Widen, R. H., Smith, J., & Friedman, H. P. (1991) · Advances in experimental medicine and biology · doi:10.1007/978-1-4684-5925-8_12 · Cited by 1 · see citing works
Self-citationImmunomodulatory properties of cannabinoids; a molecular insight
Maghembe, R. S., Mollel, J. T., & Nyandoro, S. S. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95927-8.00010-4 · Cited by 1 · see citing works
Adult Neurogenesis and Central Nervous System Cell Cycle Analysis
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Effects of Marijuana on Spleen Lymphocytes from Mice of Different Age Groups
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Self-citationCannabinoids suppress dendritic cell-induced T helper cell polarization
Lu, T. (2006) · Digital Commons - University of South Florida (University of South Florida)
Fatty acid amide hydrolase - A target for anti-inflammatory therapies?
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Suppression of human natural killer activity by delta-9-tetrahydrocannabinol
Specter, S. C. (1986) · Clinical Immunology Newsletter · doi:10.1016/0197-1859(86)90016-6
Continuous Infusion of Endotoxin Depresses Splenic Blastogenesis
Friedman, H. P., Newton, C. A., Pross, S. H., Klein, T., Widen, R. E., Vial, L. J., & Spitzer, J. A. (1992) · Immunopharmacology and Immunotoxicology · doi:10.3109/08923979209005418
Self-citationParadise, L. J., Pruitt, A., & Burgess, A. W. O. (1991) · Advances in experimental medicine and biology · doi:10.1007/978-1-4684-5925-8_14
EFFECfS OF MARUUANA ON HUMAN NATURAL KILLER CELL ACTIVITY
Specter, S. C., & Lancz, G. J. (1991)
Croxford, J. L., & Yamamura, T. (2005)
Endocannabinoid metabolism : the impact of inflammatory factors and pharmacological inhibitors
Karlsson, J. (2018) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Cannabinoid Receptor and InflammationPreprint
Osafo, N., Yeboah, K. O., Antwi, A. O., & Ainooson, G. K. (2020) · doi:10.22541/au.159986420.00633539
Molecular mechanisms of cannabinergics
Maghembe, R. S., & Mtewa, A. G. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95927-8.00012-8
Eisenstein, T. K., & Rogers, T. J. (2024) · Springer eBooks · doi:10.1007/978-3-031-68237-7_33
- Authors
- Klein, T. W., Newton, C. A., Widen, R., & Friedman, H.
- Affiliations
- University of South Florida (US)
- ORCID
- Klein, T. W.
- Venue
- Journal of Immunopharmacology
- Publisher
- Informa UK Limited
- Published
- 1985-01
- Volume
- 7
- Issue
- 4
- Pages
- 451-466
- ISSN
- 0163-0571 (ISSN-L)
- OpenAlex
- W2112279043
- Cited by
- 102
- References
- 14
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 2
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Immunopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (DA03646)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- delta-9-tetrahydrocannabinol, 11-hydroxy-THC, THC metabolites, T cell proliferation, B cell proliferation, immunosuppression, splenocytes, concanavalin A, phytohemagglutinin, lipopolysaccharide
- MeSH terms
- Animals, B-Lymphocytes, Female, Kinetics, Lymphocyte Activation, Mice, Inbred BALB C, Mitogens, T-Lymphocytes, Dronabinol, Mice, In Vitro Techniques
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