Enhanced peripheral toll-like receptor responses in psychosis: further evidence of a pro-inflammatory phenotype

Low-grade peripheral inflammation is often present in psychotic patients. Toll-like receptors (TLRs) are pattern-recognition molecules that initiate inflammation. Our objective was to investigate the peripheral TLR activity in psychosis. Forty schizophrenia patients, twenty bipolar patients and forty healthy controls (HC) were recruited. Donated whole blood was cultured with TLR agonists for 24 h. Cell supernatants were analysed using a multiplex enzyme-linked immunosorbent assay approach to measure IL-1β, IL-6, IL-8 and tumour necrosis factor-α (TNFα). Plasma was analysed for cytokines, cortisol and acute phase proteins. Here, we show that selective TLR agonist-induced cytokine (IL-1β, IL-6, IL-8 and TNFα) release is enhanced in stimulated whole blood from schizophrenia and bipolar patients compared with HC. An exaggerated release of IL-1β, IL-6 and TNFα following treatment with the TLR2 agonist HKLM was detected in both disorders compared with controls. Enhanced TLR4-induced increases in IL-1β for both disorders coupled with TNFα increases for bipolar patients were observed. TLR8-induced increases in IL-1β for both disorders as well as IL-6 and TNFα increases for bipolar patients were detected. TLR9-induced increases in IL-8 for schizophrenia patients were also observed. No differences in TLR1, TLR3, TLR5, TLR6 or TLR7 activity were detected. Plasma levels of IL-6 were significantly elevated in bipolar patients while TNFα levels were significantly elevated in schizophrenia patients compared with controls. Plasma acute phase proteins were significantly elevated in bipolar patients. These data demonstrate that specific alterations in TLR agonist-mediated cytokine release contribute to the evidence of immune dysfunction in psychotic disorders

Aqueous extract of Terminalia arjuna prevents carbon tetrachloride induced hepatic and renal disorders

BACKGROUND: Carbon tetrachloride (CCl(4)) is a well-known hepatotoxin and exposure to this chemical is known to induce oxidative stress and causes liver injury by the formation of free radicals. Acute and chronic renal damage are also very common pathophysiologic disturbances caused by CCl(4). The present study has been conducted to evaluate the protective role of the aqueous extract of the bark of Termnalia arjuna (TA), an important Indian medicinal plant widely used in the preparation of ayurvedic formulations, on CCl(4 )induced oxidative stress and resultant dysfunction in the livers and kidneys of mice. METHODS: Animals were pretreated with the aqueous extract of TA (50 mg/kg body weight) for one week and then challenged with CCl(4 )(1 ml/kg body weight) in liquid paraffin (1:1, v/v) for 2 days. Serum marker enzymes, namely, glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) were estimated in the sera of all study groups. Antioxidant status in both the liver and kidney tissues were estimated by determining the activities of the antioxidative enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST); as well as by determining the levels of thiobarbutaric acid reactive substances (TBARS) and reduced glutathione (GSH). In addition, free radical scavenging activity of the extract was determined from its DPPH radical quenching ability. RESULTS: Results showed that CCl(4 )caused a marked rise in serum levels of GPT and ALP. TBARS level was also increased significantly whereas GSH, SOD, CAT and GST levels were decreased in the liver and kidney tissue homogenates of CCl(4 )treated mice. Aqueous extract of TA successfully prevented the alterations of these effects in the experimental animals. Data also showed that the extract possessed strong free radical scavenging activity comparable to that of vitamin C. CONCLUSION: Our study demonstrated that the aqueous extract of the bark of TA could protect the liver and kidney tissues against CCl(4)-induced oxidative stress probably by increasing antioxidative defense activities