Peer-Reviewed Journal Details
Mandatory Fields
McKernan DP, Dennison U, Gaszner G, Cryan JF, Dinan, TG
2011
August
Translational Psychiatry
Enhanced peripheral toll-like receptor responses in psychosis: further evidence of a pro-inflammatory phenotype
Published
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Optional Fields
bipolar disorder inflammation schizophrenia toll-like receptor PITUITARY-ADRENAL AXIS BIPOLAR DISORDER PRENATAL INFECTION IMMUNE SUPPRESSION SCHIZOPHRENIA STRESS DEPRESSION EXPRESSION REMISSION CYTOKINES
1
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-1 beta, IL-6, IL-8 and tumour necrosis factor-alpha (TNF alpha). Plasma was analysed for cytokines, cortisol and acute phase proteins. Here, we show that selective TLR agonist-induced cytokine (IL-1 beta, IL-6, IL-8 and TNF alpha) release is enhanced in stimulated whole blood from schizophrenia and bipolar patients compared with HC. An exaggerated release of IL-1 beta, IL-6 and TNF alpha following treatment with the TLR2 agonist HKLM was detected in both disorders compared with controls. Enhanced TLR4-induced increases in IL-1 beta for both disorders coupled with TNF alpha increases for bipolar patients were observed. TLR8-induced increases in IL-1 beta for both disorders as well as IL-6 and TNF alpha 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 TNF alpha 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. Translational Psychiatry (2011) 1, e36; doi:10.1038/tp.2011.37; published online 30 August 2011
ARTN e36
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