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 me 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 mu M). Treatment of TMEV-infected astrocytes with 10 mu M 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. (C) 1998 Federation of European Biochemical Societies.