Article

Circulating interleukin-10 and interleukin-12 in Parkinson's disease.

Department of Neurology, School of Medicine, Athens National University, Athens, Greece.
Acta Neurologica Scandinavica (impact factor: 2.47). 10/2008; 119(5):332-7. DOI:10.1111/j.1600-0404.2008.01103.x pp.332-7
Source: PubMed

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.

0 0
 · 
0 Bookmarks
 · 
22 Views
  • Source
    Article: Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice.
    Ravi S Akundi, Zhenyu Huang, Joshua Eason, Jignesh D Pandya, Lianteng Zhi, Wayne A Cass, Patrick G Sullivan, Hansruedi Büeler
    [show abstract] [hide abstract]
    ABSTRACT: PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice. Purified brain mitochondria of Pink1⁻/⁻ mice showed impaired Ca²+ storage capacity, resulting in increased Ca²+ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. A subpopulation of neurons in the substantia nigra of Pink1⁻/⁻ mice accumulated phospho-c-Jun, showing that Jun N-terminal kinase (JNK) activity is increased. Pink1⁻/⁻ mice 6 months and older displayed reduced DA levels associated with increased DA turnover. Moreover, Pink1⁻/⁻ mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS), and Pink1⁻/⁻ embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB) activity. Quantitative transcriptional profiling in the striatum revealed that Pink1⁻/⁻ mice differentially express genes that (i) are upregulated in animals with experimentally induced dopaminergic lesions, (ii) regulate innate immune responses and/or apoptosis and (iii) promote axonal regeneration and sprouting. Increased mitochondrial Ca²+ sensitivity and JNK activity are early defects in Pink1⁻/⁻ mice that precede reduced DA levels and abnormal DA homeostasis and may contribute to neuronal dysfunction in familial PD. Differential gene expression in the nigrostriatal system of Pink1⁻/⁻ mice supports early dopaminergic dysfunction and shows that Pink1 deletion causes aberrant expression of genes that regulate innate immune responses. While some differentially expressed genes may mitigate neurodegeneration, increased LPS-induced brain cytokine expression and impaired cytokine-induced NF-κB activation may predispose neurons of Pink1⁻/⁻ mice to inflammation and injury-induced cell death.
    PLoS ONE 01/2011; 6(1):e16038. · 4.09 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

19 healthy subjects
 
activated blood monocytes
 
glial cells
 
heterodimeric cytokine
 
immune reactions
 
immunological disturbances
 
increases production
 
mononuclear phagocytes
 
neuroprotective effect
 
neuroprotective mechanisms
 
Parkinson's disease
 
pathogenetic mechanisms
 
pleiotropic cytokine
 
proinflammatory cytokine
 
proinflammatory cytokines
 
Recent studies
 
T cells
 
treatment status
 
UPDRS III score
 
Yahr stage