The profile of immune modulation by cannabidiol (CBD) involves deregulation of nuclear factor of activated T cells (NFAT)

Biochem Pharmacol. 2008 Sep 15;76(6):726-37. doi: 10.1016/j.bcp.2008.06.022. Epub 2008 Jul 8.

Abstract

Cannabidiol (CBD) is a cannabinoid compound derived from Cannabis Sativa that does not possess high affinity for either the CB1 or CB2 cannabinoid receptors. Similar to other cannabinoids, we demonstrated previously that CBD suppressed interleukin-2 (IL-2) production from phorbol ester plus calcium ionophore (PMA/Io)-activated murine splenocytes. Thus, the focus of the present studies was to further characterize the effect of CBD on immune function. CBD also suppressed IL-2 and interferon-gamma (IFN-gamma) mRNA expression, proliferation, and cell surface expression of the IL-2 receptor alpha chain, CD25. While all of these observations support the fact that CBD suppresses T cell function, we now demonstrate that CBD suppressed IL-2 and IFN-gamma production in purified splenic T cells. CBD also suppressed activator protein-1 (AP-1) and nuclear factor of activated T cells (NFAT) transcriptional activity, which are critical regulators of IL-2 and IFN-gamma. Furthermore, CBD suppressed the T cell-dependent anti-sheep red blood cell immunoglobulin M antibody forming cell (anti-sRBC IgM AFC) response. Finally, using splenocytes derived from CB1(-/-)/CB2(-/-) mice, it was determined that suppression of IL-2 and IFN-gamma and suppression of the in vitro anti-sRBC IgM AFC response occurred independently of both CB1 and CB2. However, the magnitude of the immune response to sRBC was significantly depressed in CB1(-/-)/CB2(-/-) mice. Taken together, these data suggest that CBD suppresses T cell function and that CB1 and/or CB2 play a critical role in the magnitude of the in vitro anti-sRBC IgM AFC response.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cannabidiol / metabolism
  • Cannabidiol / pharmacology*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunoglobulin M / biosynthesis
  • Immunologic Factors / deficiency
  • Immunologic Factors / pharmacology*
  • Interferon-gamma / immunology
  • Interleukin-2 / immunology
  • Jurkat Cells
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NFATC Transcription Factors / antagonists & inhibitors*
  • NFATC Transcription Factors / physiology
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / physiology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / physiology

Substances

  • Immunoglobulin M
  • Immunologic Factors
  • Interleukin-2
  • NFATC Transcription Factors
  • Cannabidiol
  • Interferon-gamma