The endogenous cannabinoid anandamide potentiates interleukin-6 production by astrocytes infected with Theiler's murine encephalomyelitis virus by a receptor-mediated pathway.
Theiler's murine encephalomyelitis virus (TMEV) infection of a susceptible strain of mice results in virus persistence in the brain and chronic primary immune-mediated demyelination, which resembles multiple sclerosis. Recent attention has focused on the anti-inflammatory and immunosuppressive properties of interleukin-6, a pleiotropic cytokine involved in the regulation of immunological responses, acute phase protein production and hematopoiesis. Anandamide (arachidonoyl ethanolamine) is a natural brain constituent that binds a specific brain cannabinoid receptor. In this study we investigated whether anandamide can modify interleukin-6 production by primary cultures of murine brain cortical astrocytes infected with TMEV. Astrocytes from susceptible (SJL/J) and resistant (BALB/c) strains of mice infected with TMEV (10(5)PFU/well) increased IL-6 release over a period of 24 h. Anandamide caused an enhancement of the release of IL-6 by TMEV-infected astrocytes in a concentration-dependent manner (1-25 microM). Treatment of TMEV-infected astrocytes with 10 microM arachidonyl trifluoromethyl ketone, a potent inhibitor of the amidase that degrades anandamide, was found to potentiate the effects of anandamide on IL-6 release. A novel and selective cannabinoid receptor antagonist, SR 141617A, blocked the enhancing effects of anandamide on IL-6 release by TMEV-infected astrocytes, suggesting a cannabinoid receptor-mediated pathway. The physiological implications of these results are unknown, but may be related to the hypothesis of the protective effects of cannabinoids on neurological disorders like multiple sclerosis.
Molina-Holgado
F
F
Neural Plasticity Department, Instituto Cajal, CSIC, Madrid, Spain.
Molina-Holgado
E
E
Guaza
C
C
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001253:Astrocytes / Q000378:metabolism* / Q000821:virology*; D002186:Cannabinoids / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D063388:Endocannabinoids; D005455:Fluorescent Antibody Technique; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D011051:Poliomyelitis / Q000821:virology; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000502:physiology*; D017945:Theilovirus / Q000502:physiology*
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D015850:Interleukin-6; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C078814:anandamide