Effects of olanzapine on LPS-induced inflammation in rat primary glia cells

Olanzapine (OLZ) is an atypical antipsychotic drug that also has mood-stabilizing effects. The mechanism of action of OLZ is not fully understood. Accumulating data suggest that inflammation plays a role in the pathophysiology of mental disorders and that psychotropic drugs exhibit some anti-inflammatory properties. This study was undertaken to examine the effects of OLZ on LPS-induced inflammation in rat primary glia cells. Glia cells were extracted from newborn rat brains. OLZ (1 or 50 μM) was added to culture medium at 6 or 72 h before addition of LPS for another 18 h, and levels of IL-10, prostaglandin (PG) E₂, NO and TNF-α, and expression of cyclo-oxygensase (COX)-2 and inducible NO synthase (iNOS) were determined. Treatment with 50 μM OLZ (but not 1 μM) significantly decreased LPS-induced secretion of IL-10, PGE₂ and TNF-α. In contrast, 50 μM OLZ significantly increased NO levels. OLZ did not alter the expression of COX-2 or iNOS in LPS-treated cells. These results suggest that OLZ differently affects the secretion of inflammatory mediators. Most of the significant effects of OLZ were obtained when 50 μM was used, which is a high and probably therapeutically irrelevant concentration. Therefore, under the conditions used in the present study OLZ seemed to lack a potent anti-inflammatory effect.