Suppression of experimental autoimmune encephalomyelitis by Δ8-tetrahydrocannabinol

SUPPRESSION OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS BY AS-TETRAHYDROCANNABINOL I. Wirguin, R. Mechoulam, O. A b r a m s k y and T, Brenner. Dept. of Neurology, Hadassah University Hospital and Dept. of Natural products, Hebrew University School of Pharmacy, Jerusalem, Israel. A9 Tetrahydrocannabinol (A9-THC), and other cannabinoi~, were recently shown to have many effects other than their well known psychotropic action. These include multiple modulating effects on immune function. As these substances cross readily into the central nervous system (CNS), their influence on immune mediated disorders of the CNS is of interest. Therefore, we tested the -';fleetof a related isomer, AS-THC, which more stable and less psychotropic than A9-THC on experimental antoitmnune encephalomyelitis (EAE). Two strains of rats were inoculated for EAE, and AS-'IHC (40 ms/k8) was administered orally or parenterally, daily from the day of induction. A~-THC completely prevented the development of EAE in both rat strains whereas 60-100% of vehicle treated animals developed mild to moderate EAE. Furthermore, in a second experiment in which due to the addition of Pertussis vaccine to the encephalitogenic regimen, exceptionally severe disease occurred in all the rots, AS-THC significantly delayed disease onset and reduced the severity of the disease. This beneficial influence only occurred with oral administration of THC and not with parenteral injection. The effect is valid in both strains but the mode of administration is of major significance. Possible immune and endocrine mechanisms of action, and relation of the psychotropic effect of caonabinoids to their ability to suppress EAE are suggested.

EFFICIENT ANTIGEN PRESENTATION BY ACTIVATED SPLENOCYTES ON MBP SPECIFIC T-CELLS IN EAE P. Henderikx (1), L. De Ryck (2), J. Raus 0,2) (1) Dr. L.'Willems Instituut (2) Limburgs Universitair Centrum, Universitaire Campus, 3590 Diepenbeek, Belgium Experimental Allergic E~.eephaiomyelitis (EAE), the animal model for Multiple Sclerosis, is a paralytic disease that can be induced by Myelin Basic Protein (MBP) and MBP specific T-cell lines. To improve the cloning of MBP specific T-cells derived from Lewis Rats a more efficient antigen presentation method was developed. We observed that antigen presentation was enhanced when Con A activated splenocytes were used as Antigen Presenting Cells (APC) in comparison with non-activated splenocytes or thymocytes commonly used. T-cell clones were obtained by limiting dilution of MBP-specific T-cell lines that had been restimulated once with MBP. The recovery of' the MBP specific clones was most efficient (6.3%) when 2.5 cellsiwell were seeded and activated splenoc.vtes were used as APC. No clones were obtained when we seeded MBP specific T-cells under the same conditions but with splenocytes as APC. Our data suggest that this specific enhancement wes riot only due to growth factors," normally secreted by activated splenocytes.