Endotoxin-induced systemic inflammation activates microglia: [(11)C]PBR28 positron emission tomography in nonhuman primates.

Hannestad J, Gallezot JD, Schafbauer T, Lim K, Kloczynski T, Morris ED, Carson RE, Ding YS, Cosgrove K.
Journal   Neuroimage.
Species  
Analytes Measured   IL-6 , IL-8
Matrix Tested   Baboon serum
Year   2012
Volume  
Page Numbers  
Application   Cytokines and Chemokines
Abstract
Microglia play an essential role in many brain diseases. Microglia are activated by local tissue damage or inflammation, but systemic inflammation can also activate microglia. An important clinical question is whether the effects of systemic inflammation on microglia mediate the deleterious effects of systemic inflammation in diseases such as Alzheimer's dementia, multiple sclerosis, and stroke. Positron Emission Tomography (PET) imaging with ligands that bind to Translocator Protein (TSPO) can be used to detect activated microglia. The aim of this study was to evaluate whether the effect of systemic inflammation on microglia could be measured with PET imaging in nonhuman primates, using the TSPO ligand [(11)C]PBR28.

METHODS: Six female baboons (Papio anubis) were scanned before and at 1h and/or 4h and/or 22h after intravenous administration of E. coli lipopolysaccharide (LPS; 0.1mg/kg), which induces systemic inflammation. Regional time-activity data from regions of interest (ROIs) were fitted to the two-tissue compartmental model, using the metabolite-corrected arterial plasma curve as input function. Total volume of distribution (V(T)) of [(11)C]PBR28 was used as a measure of total ligand binding. The primary outcome was change in V(T) from baseline. Serum levels of tumor necrosis factor alpha (TNFα), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) were used to assess correlations between systemic inflammation and microglial activation. In one baboon, immunohistochemistry was used to identify cells expressing TSPO.

RESULTS: LPS administration increased [(11)C]PBR28 binding (F(3,6)=5.1, p=.043) with a 29±16% increase at 1h (n=4) and a 62±34% increase at 4h (n=3) post-LPS. There was a positive correlation between serum IL-1β and IL-6 levels and the increase in [(11)C]PBR28 binding. TSPO immunoreactivity occurred almost exclusively in microglia and rarely in astrocytes.

CONCLUSION: In the nonhuman-primate brain, LPS-induced systemic inflammation produces a robust increase in the level of TSPO that is readily detected with [(11)C]PBR28 PET. The effect of LPS on [(11)C]PBR28 binding is likely mediated by inflammatory cytokines. Activation of microglia may be a mechanism through which systemic inflammatory processes influence the course of diseases such as Alzheimer's, multiple sclerosis, and possibly depression.

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Multiplex
V-PLEX NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX NHP IL-6 Kit
IL-6 | Non-human primate
Singleplex
V-PLEX NHP IL-8 Kit
IL-8 | Non-human primate
Singleplex
V-PLEX Plus Chemokine Panel 1 NHP Kit
Eotaxin-3, IL-8, IL-8 (HA), IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Non-human primate
Multiplex
V-PLEX Plus NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX Plus NHP IL-6 Kit
IL-6 | Non-human primate
Singleplex
V-PLEX Plus NHP IL-8 Kit
IL-8 | Non-human primate
Singleplex
V-PLEX Plus Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
Human IL-6 Antibody Bulk Product
IL-6
Human IL-8 Antibody Bulk Product
IL-8
Mouse IL-6 Antibody
IL-6
Rat IL-6 Antibody
IL-6
V-PLEX Chemokine Panel 1 Human Kit
Eotaxin, Eotaxin-3, IL-8, IL-8 (HA), IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Human
Multiplex
V-PLEX Human Cytokine 30-Plex Kit
Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Human IL-6 Kit
IL-6 | Human
Singleplex
V-PLEX Human IL-8 Kit
IL-8 | Human
Singleplex
V-PLEX Human Proinflammatory Panel I (4-Plex)
IFN-γ, IL-1β, IL-6, TNF-α | Human
Multiplex
V-PLEX Human Proinflammatory Panel II (4-Plex)
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
V-PLEX Mouse IL-6 Kit
IL-6 | Mouse
Singleplex
V-PLEX Plus Chemokine Panel 1 Human Kit
Eotaxin, Eotaxin-3, IL-8, IL-8 (HA), IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Human
Multiplex
V-PLEX Plus Human Cytokine 30-Plex Kit
Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Plus Human IL-6 Kit
IL-6 | Human
Singleplex
V-PLEX Plus Human IL-8 Kit
IL-8 | Human
Singleplex
V-PLEX Plus Human Proinflam. Panel I (4-Plex)
IFN-γ, IL-1β, IL-6, TNF-α | Human
Multiplex
V-PLEX Plus Human Proinflam. Panel II (4-Plex)
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
V-PLEX Plus Mouse IL-6 Kit
IL-6 | Mouse
Singleplex
V-PLEX Plus Proinflammatory Panel 1 Human Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Multiplex
V-PLEX Plus Proinflammatory Panel1 Mouse Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, KC/GRO, TNF-α | Mouse
Multiplex
V-PLEX Plus Rat IL-6 Kit
IL-6 | Rat
Singleplex
V-PLEX Proinflammatory Panel 1 Human Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Multiplex
V-PLEX Proinflammatory Panel 1 Mouse Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, KC/GRO, TNF-α | Mouse
Multiplex
V-PLEX Rat IL-6 Kit
IL-6 | Rat
Singleplex
Chemokine Panel 1 Human Control Pack
Eotaxin, Eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, MDC, TARC | Human
Proinflammatory Panel 1 Human Control Pack
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Proinflammatory Panel 1 Mouse Control Pack
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, KC/GRO, TNF-α | Mouse
Proinflammatory Panel 1 Rat Control Pack
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO, TNF-α | Rat
Human ProInflammatory-4 II Tissue Culture Kit
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
Human IL-6 Tissue Culture Kit
IL-6 | Human
Singleplex
Human ProInflammatory 7-Plex Tissue Culture Kit
IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, TNF-α | Human
Multiplex
Human ProInflammatory 9-Plex Tissue Culture Kit
GM-CSF, IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, TNF-α | Human
Multiplex
Human IL-8 Tissue Culture Kit
IL-8 | Human
Singleplex
Human ProInflammatory-4 I Tissue Culture Kit
IFN-γ, IL-1β, IL-6, TNF-α | Human
Multiplex
Human TH1/TH2 10-Plex Tissue Culture Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Multiplex
Canine ProInflammatory Panel 3 Ultra-Sensitive Kit
IL-2, IL-6, IL-8, TNF-α | Canine
Multiplex
MA6000 Rat IL-6 384 Tissue Culture Kit
IL-6 | Rat
Singleplex
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