ANANDAMIDE SUPPRESSES NITRIC-OXIDE AND TNF-ALPHA RESPONSES TO THEILERS-VIRUS OR ENDOTOXIN IN ASTROCYTES

ASTROCYTES are an important cell population in the CNS, involved in cy tokine homeostasis and participating in a variety of important physiol ogical and pathological processes. In the present study we showed that primary cultures of neonatal mouse cortical astrocytes stimulated wit h lipopolysaccharide (Balb/c mice strain, LPS: 1 mu g/ml, 18 h) or The iler's virus, TMEV (SJL/J mice strain, TMEV: 10(5) PFU/well, 24h) rele ased an increased amount of nitrites (NO2-) and tumour necrosis factor -alpha (TNF-alpha) into the culture medium. Exogenous cannabinoids are known to modulate the function of immune cells. Anandamide, an endoge nous ligand for the cannabinoid receptor, blocked the release of NO2- and TNF-alpha induced by LPS in a dose-dependent manner. In TMEV-stimu lated astrocytes anandamide also suppressed, in a dose-related manner, the stimulatory effects of TMEV on both NO2- and TNF-alpha. It is sug gested that anandamide exerts an immunoregulatory role in the CNS. The se results could have important implications in the modulation of immu nological and inflammatory processes by cannabinoid agents.