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.
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ABSTRACT: The pathophysiology of Parkinson's disease (PD) has not yet been completely elucidated. However, during the past few years, significant progress has been made in understanding the intra- and extracellular mechanisms by which proteins such as alpha-synuclein and neuroinflammatory molecules may display impaired function and/or expression in PD. Recent developments in imaging techniques based on positron emission tomography (PET) and single photon emission computed tomography (SPECT) now allow the non-invasive tracking of such molecular targets of known relevance to PD in vivo. This article summarizes recent PET and SPECT studies of new radiopharmaceuticals and discusses their potential role and perspectives for use in the fields of new drug development and early diagnosis for PD, as well to aid in differential diagnosis and monitoring of the progression of PD.Journal of Parkinson's disease. 08/2013;
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ABSTRACT: Neuroinflammation is common in neurodegenerative diseases including Parkinson disease (PD), but the extent of the process and their regional differences are not fully documented. Expression of twenty-five mRNAs was assessed with TaqMan-PCR including members of the complement system (C1QL1, C1QTNF7, C3AR1), colony stimulating factors (CYBA, CST7, INPP5D, CSF1R and CSF3R), Toll family (TLR4, TLR7), cytokines IL8, IL6, IL6ST, IL1B, TNFα family (TNFRSF1A and TNF), IL10 (IL10, IL10RA, IL10RB), TGFβ family (TGFβ1, TGFβ2), cathepsins (CTSS and CTSC) and integrin family (CLEC7A, ITGB2), in the substantia nigra pars compacta, putamen, frontal cortex area 8, and angular gyrus area 39, in a total of 43 controls and 56 cases with PD-related pathology covering stages 1-6 of Braak. Up-regulation of IL6ST was the only change in the substantia nigra at stages 1-2. Down-regulation of the majority of members examined occurred in the substantia nigra from stage 4 onwards. However, C3AR1, TLR7, and TNFα down-regulation, and C1QTNF7 and IL10RA up-regulation, were found in the putamen; down-regulation of CSF3R and TLR4 mRNAs, and up-regulation of CTSS, CYBA, IL10RA, and CLEC7A mRNAs in the frontal cortex; and up-regulation of C3AR1, CST7, CSF3R, IL10RA, and ITGB2 mRNAs in the angular cortex from stage 3 onwards in PD cases. Protein studies in frontal cortex revealed increased IL6 expression and reduced IL-10 with ELISA, and increased IL-6 with western blotting in PD. Immunohistochemistry revealed localization of IL5, IL6, and IL17 receptors in glial cells, mainly microglia; and IL5, IL10, and M-CSF in neurons. TNFα was localized in neurons and microglia. Active NFκB were localized in the nucleus of subpopulations of neurons and glial cells mainly in substantia nigra and less frequently in putamen and cerebral cortex in PD. The present findings show that neuroinflammation in PD involves pro- and anti-inflammatory cytokines, and variegated mediators of the immune response which, at least in the immune system, have distinct often opposing functions. Neuroinflammatory responses are subject to regional variations at the same stages of PD-related pathology, thus implying that distinct inflammatory responses occur in different brain regions at the same time in particular individuals. Available information shows that altered α-synuclein solubility and aggregation, Lewy body formation, oxidative damage, and neuroinflammation converge in the pathogenesis of PD.Brain Pathology 03/2014; · 4.74 Impact Factor
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ABSTRACT: Parkinson disease is an inexorably progressive neurodegenerative disorder. Multiple attempts have been made to establish therapies for Parkinson disease which provide neuroprotection or disease modification-two related, but not identical, concepts. However, to date, none of these attempts have succeeded. Many challenges exist in this field of research, including a complex multisystem disorder that includes dopaminergic and non-dopaminergic features; poorly understood and clearly multifaceted disease pathogenic mechanisms; a lack of reliable animal models; an absence of effective biomarkers of disease state, progression, and target engagement; and the confounding effects of potent symptomatic therapy. In this article, we will review previous, ongoing, and potential future trials designed to alter the progressive course of the disease from the perspective of the targeted underlying pathogenic mechanisms.Journal of the American Society for Experimental NeuroTherapeutics 10/2013; · 5.38 Impact Factor