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.
"Noteworthy, IL-10 is thought to be neuroprotective, while IL-12 is considered a pro-inflammatory cytokine . These results suggest a controlled production of these two molecules in PD pathology, where IL-10 is upregulated when IL-12 levels tends to be increased . Hence, due to the ability of IL-12 in binding in cells that mediate inflammation, Annovazzi and colleagues labelled a food and drug administration (FDA)-approved nonradioactive recombinant human IL-12 (rhIL-12) with 99m Tc ( 99m Tc-IL-12) and evaluated it in a mouse model to detect inflammation . "
[Show abstract][Hide abstract] 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.
"IL-10 is a key orchestrator of the immune system with potent anti-inflammatory effects. An increase in IL-10 concentration in the peripheral blood was previously demonstrated in other neurodegenerative disorders, such as PD and HD [26,27]. Although it is less severe, FXTAS shares features with HD including trinucleotide-repeat expansions, the presence of intranuclear inclusions, abnormal movements and cognitive decline. "
[Show abstract][Hide abstract] ABSTRACT: Background
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited late-onset neurodegenerative disorder, characterized both by neurological and cognitive deficits. It is caused by the expansion of CGG repeats (55 to 200 repeats) in the noncoding region of the fragile X mental retardation 1 (FMR1) gene. Abnormal immunological patterns are often associated with neurodegenerative disorders and implicated in their etiology. We therefore investigated the immune status of FXTAS patients, which had not been assessed prior to this study.
Peripheral blood mononuclear cells (PBMCs) were collected from 15 asymptomatic FMR1 premutation carriers and 20 age-matched controls. Concentrations of three cytokines (IL-6, IL-8, IL-10) were measured in PBMC supernatants using ELISA assays.
We found a significant increase in the concentration of the major anti-inflammatory cytokine IL-10 in supernatants of PBMCs derived from premutation carriers, when compared with controls (P = 0.019). This increase correlated significantly with the number of CGG repeats (P = 0.002).
Elevated IL-10 levels were observed in all premutation carriers, before appearance of the classical neurological symptoms; therefore, IL-10 may be one of the early biomarkers of FXTAS.
Journal of Neuroinflammation 10/2012; 9(1):238. DOI:10.1186/1742-2094-9-238 · 5.41 Impact Factor
"Markedly increased proinflammable cytokines: TNF-a, interleukines 1ß (IL-1ß), IL-2, IL-4, IL-6 in the ventricular and lumbar cerebrospinal fluid (CSF) were found in PD patients . Previous studies also found an elevated level of interleukins and TNF-a in serum of the patients with PD and indicated a role of peripheral dysregulation in the cytokine network associated with PD  . Cytokines produced in the brain could diffuse across the bloodbrain barrier into the peripheral tissue or could be produced peripherally by general inflammation. "
[Show abstract][Hide abstract] ABSTRACT: Introduction:
The role of inflammatory factors in Parkinson's disease (PD) has not been consistently proven yet. Despite the presence of some potentially causative factors, the primary and initiating factor has not been determined. Therefore the influence of proinflammatory and antiphlogistic factors on the risk of PD remains unclear. The aim of the study was to evaluate the level of NT-proCNP as well as proinflammatory factors in peripheral blood of patients with PD and to compare the changes of cytokines and NT-proCNP profile of these patients with the profile within the control group.
Materials and methods:
The study group consisted of 60 patients with the diagnosis of idiopathic PD, in the mean age of 59 ± 15.5 years, and control group of 24 persons, in the mean age of 64 ± 5.8 years, without neurodegenerative and inflammatory disorders. The quantitative determination of cytokines was evaluated with the fluorokine MAP cytokine multiplex kit and the Luminex 100 Platform. ELISA kits were used for the quantitative determination of human NT-proCNP.
The levels of NT-proCNP and all measured cytokines were higher in serum of PD patients in comparison to the control group, though the significant differences were only observed in relation to serum level of NT-proCNP (p<0.05) and TNF-α (p<0.001). The mean serum level of NT-proCNP in PD patients correlates with the level of TNF-α (R=0.359, p<0.05) and IL-10 (R=-0.39, p=0.05). There are also other correlations in serum of PD group: between IL-10 and IL-12 (R=0.39, p=0.05), IL-6 and IL-1ß (R=0.65, p=0.05). The serum level of IL-6 is also in a positive relation with H&Y stage (R=0.27, p=0.05).
The concentration of NT-proCNP and TNF-α is essentially higher in parkinsonian patients than in healthy group. The levels of other anti- and proinflammatory cytokines also tend to be higher in PD patients in comparison to the control group. It confirms the significance of these factors' influence on molecular pathogenesis of PD and makes NT-proCNP a new potential determinant of inflammation in PD patients.
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