Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the relationship between cytokines and cerebrospinal fluid (CSF) cells, we detected interferon (IFN)-gamma and interleukin (IL)-6 producing cells in CSF from the patients with central nervous system (CNS) infectious diseases by immunocytochemistry. Five CSF cell smears from three herpes encephalitis patients, three from a patient with EB virus radiculoneuritis, four from the three patients with purulent meningitis, five from five patients with viral meningitis were obtained during early or subacute stages of diseases. Control CSF cell smears were taken from twenty seven patients with motor neuron disease, Parkinson's disease and spinocerebellar degeneration. Immunocytochemistry using specific polyclonal anti-IFN-gamma and IL-6 sera were used to detect each producing cell. Simultaneously, individual positively immuno-reactive cells were morphologically classified macrophage or lymphocyte. The IFN-gamma positive cells immunostained with specific antibody showed brown-colored deposits within the cytoplasm whereas no deposit was in the nucleus (Fig. 1). These phenotype of IFN-gamma positive cells were considered to be lymphocytes or macrophages. However, IFN-gamma-positive macrophages were predominantly seen at the early stages of herpes simplex encephalitis and purulent meningitis. The percent of IFN-gamma positive cells in total CSF cells obtained from the patients with the CNS infectious diseases was 2.3-38.7 as shown in Table 1. The IL-6 positive cells (Fig. 2) were also found early in the course and in subacute stages in the CNS infectious diseases and ranged from 2.5-50 percent in total CSF cells (Table 1). In contrast neither IFN-gamma- nor IL-6-positive cells were detected in non-inflammatory diseases (Table 1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Detection of interferon-gamma and IL-6 producing cells in cerebrospinal fluid cells in the central nervous system infectious diseases using immunocytochemistry]. 149 Mar 21

Interleukin (IL)-1 beta, IL-6, epidermal growth factor (EGF), and transforming growth factor-alpha (TGF-alpha) were measured for the first time in the brain (caudate nucleus, putamen and cerebral cortex) from control and parkinsonian patients by highly sensitive sandwich enzyme immunoassays. The concentrations of IL-1 beta, IL-6, EGF, and TGF-alpha in the dopaminergic, striatal regions were significantly higher in parkinsonian patients than those in controls, whereas those in the cerebral cortex did not show significant differences between parkinsonian and control subjects. Since these cytokines and growth factors may play important roles as neurotrophic factors in the brain, the present results suggest that they may be produced as compensatory responses in the nigrostriatal dopaminergic regions in Parkinson's disease, and may be related, at least in part, to the process of neurodegeneration in Parkinson's disease.
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PMID:Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. 770 May 68

The pathogenesis of Parkinson's disease (PD) is largely unknown. Recently, several studies have presented evidence of an immunological dysfunction in patients suffering from PD. We studied the immune responsiveness of patients with idiopathic PD (n = 20) by investigation of the ability of peripheral blood mononuclear cells to produce cytokines after mitogenic stimulation in a whole blood assay. A group of age-related healthy blood donors served as control (n = 19). Additionally, white blood count, leukocyte differentiation and lymphocyte subtyping were performed. PD patients had a significantly higher neutrophil count, but analysis of T-cell subsets showed no difference between the two groups. In peripheral blood, secretion of interleukin-2 (IL-2) after mitogenic stimulation was significantly diminished in the patients' group (p < 0.01), whereas values of IFN-alpha 2, IL-6, IFN-gamma and sIL-2R were comparable in both groups. IL-2 production correlated negatively with the mean annual dose of levodopa treatment and correlated significantly (p < 0.002) with amantadine uptake. Analysis of sex, age, duration of illness and other drug intake revealed no correlation with cytokine release. Our findings support the view that there is a selective abnormality in the immune repertoire of peripheral blood lymphocytes in patients suffering from PD, the reasons for which need to be explored.
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PMID:Defective production of interleukin-2 in patients with idiopathic Parkinson's disease. 858 16

Interleukin (IL)-1 beta , IL-2, IL-4, IL-6, epidermal growth factor (EGF), and transforming growth factor (TGF)-alpha were measured for the first time in ventricular cerebrospinal fluid (VCSF) from control non-parkinsonian patients, patients with juvenile parkinsonism (JP) and patients with Parkinson's disease (PD) by highly sensitive sandwich enzyme immunoassays. All cytokines were detectable in VCSF from control and parkinsonian patients, and the concentrations were much higher than those in lumbar CFS. The concentrations of IL-1 beta, IL-2, IL-4 and TGF-alpha in VCSF were higher in JP than those in controls (P < 0.05). In contrast, the concentrations of IL-2 and IL-6 in VCSF from patients with PD were higher than those from control patients (P < 0.05). These results agree with our previous reports, in which the cytokine levels were elevated in the striatal dopaminergic region of the brain from patients with PD. Since VCSF is produced in the ventricles, the alteration of cytokines in VCSF may reflect the changes of cytokines in the brain. Because cytokines play an important role as mitogens and neurotrophic factors in the brain, the increases in cytokines as a compensatory response may occur in the brain of patients of JP or PD during the progress of neurodegeneration. Increase in cytokines may contribute not only as a compensatory response but as a primary initiating trigger for the neurodegeneration.
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PMID:Interleukin (IL)-1 beta, IL-2, IL-4, IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson's disease. 880 36

The search for specific neurotrophic factors that will eventually be used to reduce or arrest the rate of degeneration of dopaminergic neurons in Parkinson's disease is being pursued by first testing the ability of putative compounds to increase the survival of dopaminergic neurons in primary cultures of the fetal, ventral mesencephalon. This research has intensified in recent years. The experimental procedures used by different laboratories in these studies differ widely, and meaningful comparisons of the results obtained are accordingly difficult to make. Some important experimental variables include the age of the fetal tissue used; the dissection technique used to isolate the ventral mesencephalon; the percentage of dopaminergic neurons present in the culture initially; handling of the tissue during dissection; the technique used to disperse the cells; the use of serum; the technique of plating the cells; the attachment factors used; detachment and loss of cells during the staining procedure; the age of the cultures at the time of analysis; the uneven distribution of cells at the time of analysis and the use of imaging techniques in the analysis. We show that when the E14 rat embryo is used, it is possible to consistently obtain a culture with 20% of tyrosine hydroxylase-positive neurons. Neither the plating density in the range of 7.8 x 10(3) to 1.25 x 10(5) cells/cm2, nor the percentage of serum in the growth medium affected the percentage of cells that expressed TH initially, at 4 or 12 h after plating. When the cells were plated as 25 microliters droplets, called microislands (area approximately 12.5 mm2), and allowed to attach before additional growth medium was added, cell density remained uniform at the center of the microisland for the duration of the culture. Restriction of the analysis of cell survival to the center of the microisland therefore helped to decrease the variability in counting that could occur when cells are dispersed over a larger area. In contrast, in an 8-well chamber slide or 35 mm petri dish, in which the whole area is plated, cell density was consistently higher at the edge (edge effect), versus the centre, by a factor of about three. The use of microisland cultures also has the additional benefit of increasing by a factor of about five the number of individual cultures that can be set up per liter, and a proportionate reduction in the number of animals used per experiment. When the percentage of serum in the growth medium was 0% always, or 10% for the first 12 h, and 0% thereafter, or 10% always, the number of TH-pos neurons per field (using a x 20 objective, column factor 1.25; area 320 microns2) after 5 days in culture (DIV5) was < 1,3-8 and 14-22, respectively. Under the same experimental conditions, the number of neurons (MAP2-positive) per field was 5-8, 18-30 and 45-65 (N = 10 in all cases), respectively. Serum deprivation therefore has a highly deleterious effect on neuronal survival in culture. We suggest that cultures that were exposed to serum at any stage of the experiment, should not be referred to as "serum-free', since even a brief exposure to serum exerts a protective effect on neurons, and especially on dopaminergic neurons. Instead, the percentage and kind of serum used, the exact usage, and the duration of exposure of the cells to serum should be stated. Finally, it is suggested that where possible, an imaging system with manual count and journaling capabilities be used in the analysis. The methods described are illustrated by dose-response curves of the neurotrophic effects of BDNF, NGF-beta and IL-6 versus percentage survival on dopaminergic neurons, when grown in serum-free medium throughout.
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PMID:Standardized methods to bioassay neurotrophic factors for dopaminergic neurons. 884 22

Parkinson's disease (PD) is characterized by a markedly decreased number of nigrostriatal dopaminergic neurons. The pathogenesis of PD is still unknown; among other etiological factors, immunological abnormalities have been suggested. Recently, interleukin-2 (IL-2) has been hypothesized to be an endogenous cytokine that regulates striatal dopaminergic function. We examined the plasma concentrations of IL-1, IL-2, IL-6 and blood levels of ACTH, cortisol and prolactin of 21 patients with PD without any previous treatment. Age- and sex-matched subjects without any neurological or immune disorders were used as controls. Significantly higher serum concentrations of IL-2 in patients with PD were found. Treatment with antiparkinsonian drugs reduced IL-2 levels in these patients. Our results suggested a functional relationship between central dopaminergic and immune systems and a possible involvement of the latter in the pathogenesis of PD.
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PMID:Evaluation of interleukins, ACTH, cortisol and prolactin concentrations in the blood of patients with parkinson's disease. 894 28

The capacity of peripheral blood mononuclear cells (PBMC) from patients with treated Parkinson's disease (PD) to produce interleukin (IL) IL-1 beta IL-2, IL-6, tumor necrosis factor (TNF)-alpha and the proliferative response to mitogens, was compared with that from cells from healthy subjects. The production of IL-2 and the mitogen response were significantly lower in PD patients, whereas the secretion of IL-1 beta, IL-6 and TNF-alpha were significantly enhanced. To evaluate the role of levodopa in creating immunological alterations, PBMC of patients and controls were incubated with concentrations of the drug extrapolated from those used in clinical practice. Levodopa caused an inhibition of mitogen-induced proliferation, stimulation of IL-6 and TNF-alpha production, whereas the secretion of IL-1 beta and IL-2 was not affected. The results of the study provide a further support for the interrelationship between the central nervous and immune system. In addition, the data indicate that the immunological alterations found in PD may be partially attributed to levodopa administration.
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PMID:IL-1 beta, IL-2, IL-6 and TNF-alpha production by peripheral blood mononuclear cells from patients with Parkinson's disease. 1034 2

The etiology of Parkinson's disease is not known. Nevertheless, a significant body of biochemical data from human brain autopsy studies and from animal models points to an ongoing process of oxidative stress in the substantia nigra, which could initiate dopaminergic neurodegeneration. It is not known whether oxidative stress is a primary or secondary event. Oxidative stress, as induced by the neurotoxins 6-hydroxydopamine and MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), has been used in animal models to investigate the process of neurodegeneration to facilitate the development of antioxidant, neuroprotective drugs. It is apparent in these animal models that radical scavengers, iron chelators, dopamine agonists, nitric oxide synthase inhibitors and certain calcium channel antagonists provide neuroprotection against such toxins if given prior to the insult. Furthermore, recent work from human and animal studies has provided evidence of an inflammatory process. This expresses itself as proliferation of activated microglia in the substantia nigra, activation and translocation of transcription factors and neurotrophic factor (NF), kappa-beta and elevation of cytotoxic cytokines, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. Both radical scavengers and iron chelators prevent lipopolysaccharide (LPS) and iron-induced activation of NF kappa-beta. If an inflammatory response is involved in Parkinson's disease, it would be logical to consider antioxidants and the newly developed, non-steroidal, anti-inflammatory drugs such as cyclo-oxygenase (COX2) inhibitors as a form of treatment. However, to date there has been little or no success in the clinical treatment of neurodegenerative diseases (for example, Parkinson's disease, ischaemia etc.) where neurons die, while in animal models the same drugs provide neuroprotection. This may indicate that either the animal models employed do not reflect the events in neurodegenerative diseases, or that because neuronal death involves a cascade of events, a single neuroprotective drug is not effective. Thus, consideration should be given to multi-neuroprotective drug therapy in Parkinson's disease, similar to the approach taken in AIDS and cancer therapy.
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PMID:MPTP and 6-hydroxydopamine-induced neurodegeneration as models for Parkinson's disease: neuroprotective strategies. 1099 72

We found that in Parkinson's disease (PD) the levels of various cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-2, IL-4, IL-6, epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, TGF-beta1] were significantly increased in the striatum (caudate and putamen) of the postmortem brain and in ventricular or spinal cerebrospinal fluid (VCSF, LCSF). Furthermore, the levels of the apoptosis-related proteins such as bcl-2 and soluble Fas (sFas) in the striatum were also elevated in PD. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated parkinsonism mice, the levels of IL-1beta in the striatum were significantly increased, but those of nerve growth factor (NGF) were significantly decreased, compared with control mice. In hemiparkinsonism rats produced by injection of 6-hydroxydopamine (6-OHDA) into one side of the median forebrain bundle, the levels of TNF-alpha in the 6-OHDA-treated side were increased in the striatum and substantia nigra, but not in the cerebral cortex, compared with those in the control side. Repeated administration of L-DOPA in the 6-OHDA-treated rats did not change the TNF-alpha levels in the control side and in the 6-OHDA-treated side in the substantia nigra, striatum, and cerebral cortex. Our results suggest that the changes in the levels of cytokines, neurotrophins, and apoptosis-related proteins in the nigrostriatal regions of PD may be involved in apoptosis and degeneration of the nigrostriatal DA neurons.
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PMID:Cytokines in Parkinson's disease. 1112 4

Low rates of coronary heart disease was found in Greenland Eskimos and Japanese who are exposed to a diet rich in fish oil. Suggested mechanisms for this cardio-protective effect focused on the effects of n-3 fatty acids on eicosanoid metabolism, inflammation, beta oxidation, endothelial dysfunction, cytokine growth factors, and gene expression of adhesion molecules; But, none of these mechanisms could adequately explain the beneficial actions of n-3 fatty acids. One attractive suggestion is a direct cardiac effect of n-3 fatty acids on arrhythmogenesis. N-3 fatty acids can modify Na+ channels by directly binding to the channel proteins and thus, prevent ischemia-induced ventricular fibrillation and sudden cardiac death. Though this is an attractive explanation, there could be other actions as well. N-3 fatty acids can inhibit the synthesis and release of pro-inflammatory cytokines such as tumor necrosis factoralpha (TNFalpha) and interleukin-1 (IL-1) and IL-2 that are released during the early course of ischemic heart disease. These cytokines decrease myocardial contractility and induce myocardial damage, enhance the production of free radicals, which can also suppress myocardial function. Further, n-3 fatty acids can increase parasympathetic tone leading to an increase in heart rate variability and thus, protect the myocardium against ventricular arrhythmias. Increased parasympathetic tone and acetylcholine, the principle vagal neurotransmitter, significantly attenuate the release of TNF, IL-1beta, IL-6 and IL-18. Exercise enhances parasympathetic tone, and the production of anti-inflammatory cytokine IL-10 which may explain the beneficial action of exercise in the prevention of cardiovascular diseases and diabetes mellitus. TNFalpha has neurotoxic actions, where as n-3 fatty acids are potent neuroprotectors and brain is rich in these fatty acids. Based on this, it is suggested that the principle mechanism of cardioprotective and neuroprotective action(s) of n-3 fatty acids can be due to the suppression of TNFalpha and IL synthesis and release, modulation of hypothalamic-pituitary-adrenal anti-inflammatory responses, and an increase in acetylcholine release, the vagal neurotransmitter. Thus, there appears to be a close interaction between the central nervous system, endocrine organs, cytokines, exercise, and dietary n-3 fatty acids. This may explain why these fatty acids could be of benefit in the management of conditions such as septicemia and septic shock, Alzheimer's disease, Parkinson's disease, inflammatory bowel diseases, diabetes mellitus, essential hypertension and atherosclerosis.
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PMID:Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how? 1113 72


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