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

Abstract

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 mM) 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) E 2 , NO and TNF-a, and expression of cyclo-oxygensase (COX)-2 and inducible NO synthase (iNOS) were determined. Treatment with 50 mM OLZ (but not 1 mM) significantly decreased LPS-induced secretion of IL-10, PGE 2 and TNF-a. In contrast, 50 mM 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 mM 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.

Assessment of the Effects of Dietary Vitamin D Levels on Olanzapine-Induced Metabolic Side Effects: Focus on the Endocannabinoidome-Gut Microbiome Axis

“…Vitamin D modifies PGE 2 levels directly in different cell types [74,75], however, we did not see any changes in PGE 2 or PGD 2 levels between groups under different vitamin D diets. Previous studies have demonstrated administration of olanzapine reduces PGE 2 levels in different parts of the brain in vivo and in vitro [76,77]. While we did not observe any such changes in the hypothalamus (data not shown), we found an enhancement of PGE 2 and PGD 2 levels, particularly in the SAT.…”

Chronic olanzapine administration causes metabolic syndrome through inflammatory cytokines in rodent models of insulin resistance

“…Numerous clinical and animal studies have shown that brain inflammation is closely related to schizophrenia pathophysiology 34–37 . More interestingly, olanzapine could prevent inflammatory mediation by reducing glial activity in primary glia cells cultured from rat newborn brains 38,39 . However, female rats that received olanzapine treatment had elevated plasma levels of IL-8 and IL-1β and increased macrophage infiltration in white adipose tissue in the peripheral system.…”