Elevated levels of endocannabinoids in chronic hepatitis C may modulate cellular immune response and hepatic stellate cell activation

Int J Mol Sci. 2015 Mar 27;16(4):7057-76. doi: 10.3390/ijms16047057.


The endocannabinoid (EC) system is implicated in many chronic liver diseases, including hepatitis C viral (HCV) infection. Cannabis consumption is associated with fibrosis progression in patients with chronic hepatitis C (CHC), however, the role of ECs in the development of CHC has never been explored. To study this question, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) were quantified in samples of HCV patients and healthy controls by gas and liquid chromatography mass spectrometry. Fatty acid amide hydrolase (FAAH) and monoaclyglycerol lipase (MAGL) activity was assessed by [3H]AEA and [3H]2-AG hydrolysis, respectively. Gene expression and cytokine release were assayed by TaqMan PCR and ELISpot, respectively. AEA and 2-AG levels were increased in plasma of HCV patients, but not in liver tissues. Hepatic FAAH and MAGL activity was not changed. In peripheral blood mononuclear cells (PBMC), ECs inhibited IFN-γ, TNF-α, and IL-2 secretion. Inhibition of IL-2 by endogenous AEA was stronger in PBMC from HCV patients. In hepatocytes, 2-AG induced the expression of IL-6, -17A, -32 and COX-2, and enhanced activation of hepatic stellate cells (HSC) co-cultivated with PBMC from subjects with CHC. In conclusion, ECs are increased in plasma of patients with CHC and might reveal immunosuppressive and profibrogenic effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amidohydrolases / metabolism
  • Arachidonic Acids / blood
  • Arachidonic Acids / metabolism*
  • Cells, Cultured
  • Cytokines / metabolism
  • Endocannabinoids / blood
  • Endocannabinoids / metabolism*
  • Female
  • Glycerides / blood
  • Glycerides / metabolism*
  • Hepatic Stellate Cells / metabolism
  • Hepatic Stellate Cells / pathology*
  • Hepatitis C, Chronic / enzymology
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / pathology*
  • Humans
  • Immunity, Cellular
  • Male
  • Middle Aged
  • Monoacylglycerol Lipases / metabolism
  • Polyunsaturated Alkamides / blood
  • Polyunsaturated Alkamides / metabolism*


  • Arachidonic Acids
  • Cytokines
  • Endocannabinoids
  • Glycerides
  • Polyunsaturated Alkamides
  • glyceryl 2-arachidonate
  • Monoacylglycerol Lipases
  • Amidohydrolases
  • fatty-acid amide hydrolase
  • anandamide