Circulating interleukin-10 and interleukin-12 in Parkinson's disease.
ABSTRACT Interleukin (IL)-12 is a heterodimeric cytokine produced by activated blood monocytes, macrophages and glial cells. It enhances differentiation and proliferation of T cells and increases production of proinflammatory cytokines. IL-10 is a pleiotropic cytokine produced by both lymphocytes and mononuclear phagocytes including microglia. Recent studies demonstrated the neuroprotective effect of IL-10. There is little information about the involvement of IL-12 or IL-10 in the pathophysiology of Parkinson's disease (PD).
The objective of our study was to assess the role of IL-12 as a potential marker of immune reactions in patients with PD and to investigate whether IL-10, an immunosuppressive cytokine, may have a neuroprotective effect in the pathogenesis of PD.
We measured using immunoassay serum IL-12 and IL-10 levels in 41 patients with PD in comparison with serum levels in 19 healthy subjects (controls) age and sex matched. IL-12 and IL-10 levels were tested for correlation with sex, age, disease duration, Hoehn and Yahr stage and the UPDRS III score.
The PD group presented with significantly increased IL-10 levels when compared with the control group (P = 0.02). The increase observed was not affected by the treatment status. A strong and significant correlation between IL-10 and IL-12 levels was observed in patients with PD (R(S) = 0.7, P < 0.000001).
Our findings suggest that IL-10 may be involved in the pathogenetic mechanisms of PD. The elevation of IL-10 and the significant correlation between IL-10 and IL-12, a proinflammatory cytokine, may suggest that immunological disturbances and neuroprotective mechanisms are involved in patients with PD.
SourceAvailable from: Janelle Drouin-Ouellet[Show abstract] [Hide abstract]
ABSTRACT: Accumulating evidence supports a role for the immune system in the pathogenesis of Parkinson's disease (PD). Importantly, recent preclinical studies are now suggesting a specific contribution of inflammation to the α-synuclein (αSyn) induced pathology seen in this condition. We used flow cytometry and western blots to detect toll-like receptor (TLR) 2 and 4 expression in blood and brain samples of PD patients and mice overexpressing human αSyn. To further assess the effects of αSyn overexpression on the innate immune system, we performed a longitudinal study using Thy1.2-αSyn mice that expressed a bicistronic DNA construct (reporter genes luciferase) and green fluorescent protein) under the transcriptional control of the murine TLR2 promoter. Here, we report increases in TLR2 and TLR4 expression in circulating monocytes and of TLR4 in B cells and in the caudate/putamen of PD patients. Monthly bioluminescence imaging of Thy1.2-αSyn mice showed increasing TLR2 expression from 10 months of age, although no change in TLR2 and TLR4 expression was observed in the blood and brain of these mice at 12 months of age. Dexamethasone treatment starting at 5 months of age for one month significantly decreased the microglial response in the brain of these mice and promoted functional recovery as observed using a wheel-running activity test. Our results show that TLR2 and TLR4 are modulated in the blood and in the brain of PD patients and that overexpression of αSyn leads to a progressive microglial response, the inhibition of which as a beneficial impact on some motor phenotypes of an animal model of α-synucleinopathy. © The Author 2014. Published by Oxford University Press on behalf of CINP.
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ABSTRACT: Neuroimmune diseases have diverse symptoms and etiologies but all involve pathological inflammation that affects normal central nervous system signaling. Critically, many neuroimmune diseases also involve insufficient signaling/bioavailability of interleukin-10 (IL-10). IL-10 is a potent anti-inflammatory cytokine released by immune cells and glia, which drives the regulation of a variety of anti-inflammatory processes. This review will focus on the signaling pathways and function of IL-10, the current evidence for insufficiencies in IL-10 signaling/bioavailability in neuroimmune diseases, as well as the implications for IL-10-based therapies to treating such problems. We will review in detail four pathologies as examples of the common etiologies of such disease states, namely neuropathic pain (nerve trauma), osteoarthritis (peripheral inflammation), Parkinson's disease (neurodegeneration), and multiple sclerosis (autoimmune). A number of methods to increase IL-10 have been developed (e.g. protein administration, viral vectors, naked plasmid DNA, plasmid DNA packaged in polymers to enhance their uptake into target cells, and adenosine 2A agonists), which will also be discussed. In general, IL-10-based therapies have been effective at treating both the symptoms and pathology associated with various neuroimmune diseases, with more sophisticated gene therapy-based methods producing sustained therapeutic effects lasting for several months following a single injection. These exciting results have resulted in IL-10-targeted therapeutics being positioned for upcoming clinical trials for treating neuroimmune diseases, including neuropathic pain. Although further research is necessary to determine the full range of effects associated with IL-10-based therapy, evidence suggests IL-10 may be an invaluable target for the treatment of neuroimmune disease. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'. Copyright © 2014 Elsevier Ltd. All rights reserved.Neuropharmacology 11/2014; DOI:10.1016/j.neuropharm.2014.10.020 · 4.82 Impact Factor
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ABSTRACT: Inflammatory mediators may reflect a role of systemic inflammation in the neurodegenerative process of Parkinson's disease (PD). Interleukin-6 (IL-6) and chemokine ligand 5 (CCL5), also known as RANTES (regulated on activation, normal T cell expressed and secreted), have been implicated in neurodegenerative diseases including PD. Serum levels of RANTES and IL-6 of 78 consecutive PD patients and age-matched 80 controls were measured. Patients with PD had higher RANTES and IL-6 levels compared with the controls. We found that serum RANTES levels strongly correlated with Hoehn-Yahr score and disease duration in PD patients. This study indicated that patients with PD have an on-going systemic inflammatory profile where the elevated peripheral production of RANTES may play a role in the neurodegenerative process.