The anti-inflammatory prostaglandin 15d-PGJ2 and its nuclear receptor PPARgamma are decreased in schizophrenia

A number of findings suggest that inflammation plays a role in the pathophysiology of schizophrenia. Taking into account a physiological balance between pro- and anti-inflammatory mediators, we measured the plasma levels of cyclooxygenase-derived mediators and other key pro- and anti-inflammatory transcription factors in peripheral blood mononuclear cells (PBMC). Forty healthy subjects and 46 treated chronic schizophrenic patients with an acutely exacerbated condition who met DSM-IV criteria were included. COX by-products prostaglandin E-2 (PGE(2)) and 15d-prostaglandin J(2) (15d-PGJ(2)) plasma levels were measured by EIA. Peroxisome proliferator-activated receptor gamma (PPAR gamma) as well as nuclear factor kappaB (NF kappa B) activity in nuclear extracts from PBMC and expression of its inhibitory subunit I kappa B alpha in cytosolic extracts were determined using ELISA-based kits. Schizophrenic patients showed higher plasma levels of pro-inflammatory PGE(2) than age-matched controls (p = 0.043). On the contrary, levels of anti-inflammatory 15-d-PGJ(2) were lower (p = 0.004), correlating with a lower expression of its nuclear target. PPAR gamma in nuclear extracts from PBMC (p = 0.001). Although no changes in NF kappa B activity were observed between patients and healthy controls, the expression of its inhibitory protein I kappa B alpha was lower in the patients compared to the controls (p = 0.027). These findings suggest that schizophrenia is associated with a systemic imbalance in the plasma levels of pro-inflammatory/anti-inflammatory prostaglandins in favor of the former. Furthermore, the expression and activity of anti-inflammatory PPAR gamma are diminished in PBMC, which indicates a state of inflammation and blunted anti-inflammatory counterbalancing mechanisms at systemic level in these patients. (C) 2011 Elsevier B.V. All rights reserved.