Influence of fatty acid ethanolamides and delta9-tetrahydrocannabinol on cytokine and arachidonate release by mononuclear cells

Eur J Pharmacol. 1997 Jul 9;330(2-3):231-40. doi: 10.1016/s0014-2999(97)01007-8.


The effects of arachidonic acid ethanolamide (anandamide), palmitoylethanolamide and delta9-tetrahydrocannabinol on the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-4, interleukin-6, interleukin-8, interleukin-10, interferon-gamma, p55 and p75 TNF-alpha soluble receptors by stimulated human peripheral blood mononuclear cells as well as [3H]arachidonic acid release by non-stimulated and N-formyl-Met-Leu-Phe (fMLP)-stimulated human monocytes were investigated. Anandamide was shown to diminish interleukin-6 and interleukin-8 production at low nanomolar concentrations (3-30 nM) but inhibited the production of TNF-alpha, interferon-gamma, interleukin-4 and p75 TNF-alpha soluble receptors at higher concentrations (0.3-3 microM). Palmitoylethanolamide inhibited interleukin-4, interleukin-6, interleukin-8 synthesis and the production of p75 TNF-alpha soluble receptors at concentrations similar to those of anandamide but failed to influence TNF-alpha and interferon-gamma production. The effect of both compounds on interleukin-6 and interleukin-8 production disappeared with an increase in the concentration used. Neither anandamide nor palmitoylethanolamide influenced interleukin-10 synthesis. delta9-Tetrahydrocannabinol exerted a biphasic action on pro-inflammatory cytokine production. TNF-alpha, interleukin-6 and interleukin-8 synthesis was maximally inhibited by 3 nM delta9-tetrahydrocannabinol but stimulated by 3 microM delta9-tetrahydrocannabinol, as was interleukin-8 and interferon-gamma synthesis. The level of interleukin-4, interleukin-10 and p75 TNF-alpha soluble receptors was diminished by 3 microM delta9-tetrahydrocannabinol. [3H]Arachidonate release was stimulated only by high delta9-tetrahydrocannabinol and anandamide concentrations (30 microM). These results suggest that the inhibitory properties of anandamide, palmitoylethanolamide and delta9-tetrahydrocannabinol are determined by the activation of the peripheral-type cannabinoid receptors, and that various endogenous fatty acid ethanolamides may participate in the regulation of the immune response.

MeSH terms

  • Amides
  • Arachidonic Acid / blood
  • Arachidonic Acid / metabolism*
  • Arachidonic Acids / pharmacology*
  • Cytokines / blood
  • Cytokines / metabolism*
  • Dronabinol / pharmacology*
  • Endocannabinoids
  • Ethanolamines
  • Humans
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism*
  • Palmitic Acids / pharmacology*
  • Polyunsaturated Alkamides
  • Secretory Rate / drug effects


  • Amides
  • Arachidonic Acids
  • Cytokines
  • Endocannabinoids
  • Ethanolamines
  • Palmitic Acids
  • Polyunsaturated Alkamides
  • Arachidonic Acid
  • palmidrol
  • Dronabinol
  • anandamide