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

McKernan, D.P., Dennison, U., Gaszner, G., Cryan, J.F., Dinan, T.G.
Journal   Translational Psychiatry
Species  
Analytes Measured   CRP , IL-6 , IL-8 , SAA
Matrix Tested   Plasma, Cell culture supernatants
Year   2011
Volume   1
Page Numbers   e36
Application   Cytokines and Chemokines
Abstract
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.

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Singleplex
U-PLEX Custom Metabolic Group 1 (human) 384-well Assays
BAFF, BDNF, β-NGF, C-Peptide, CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FGF-21, FGF-23, FLT3L, Fractalkine, FSH, G-CSF, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, Insulin, IP-10, Leptin, Luteinizing Hormone (LH), MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-5, PP, Proinsulin, PYY (total), SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 | Human
Multiplex
U-PLEX Human CRP Assay
CRP | Human
Singleplex
U-PLEX Human SAA Assay
SAA | Human
Singleplex
U-PLEX Human SAA Antibody Set
SAA | Human
U-PLEX Human CRP Antibody Set
CRP | Human
S-PLEX NHP IL-6 Kit
IL-6 | Non-human primate
Singleplex
S-PLEX Human IL-6 Kit
IL-6 | Human
Singleplex
R-PLEX Mouse SAA Antibody Set
SAA | Mouse
R-PLEX Mouse CRP Antibody Set
CRP | Mouse
V-PLEX Viral Panel 3 NHP Kit
IFN-γ, IL-1β, IL-5, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Viral Panel 3 Human Kit
IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α | Human
Multiplex
V-PLEX Plus Viral Panel 3 NHP Kit
IFN-γ, IL-1β, IL-5, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Plus Viral Panel 3 Human Kit
IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α | Human
Multiplex
U-PLEX Human IL-6 Assay
IL-6 | Human
Singleplex
U-PLEX Human IL-8 Assay
IL-8 | Human
Singleplex
U-PLEX Mouse IL-6 Assay
IL-6 | Mouse
Singleplex
U-PLEX NHP IL-6 Assay
IL-6 | Non-human primate
Singleplex
U-PLEX NHP IL-8 Assay
IL-8 | Non-human primate
Singleplex
R-PLEX Mouse CRP Assay
CRP | Mouse
Singleplex
R-PLEX Rat IL-6 Assay
IL-6 | Rat
Singleplex
R-PLEX Mouse SAA Assay
SAA | Mouse
Singleplex
R-PLEX Rat IL-6 Antibody Set
IL-6 | Rat
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