Interleukin (IL)-1β, IL-2, IL-4, IL-6 and transforming growth factor-α levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson's disease
Abstract
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Increased levels of inflammatory cytokines including IL-1β, IL-6, IFN-γ, and TNF-α are found in brain parenchyma and cerebrospinal fluid of Parkinson's disease patients.
“Furthermore, increased levels of inflammatory cytokines including interleukin 1-beta (IL-1β), interleukin-6 (IL-6), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) have been found within brain parenchyma and human cerebrospinal fluid (CSF) of PD patients [7–9].”
From Intrastriatal injection of preformed alpha-synuclein fibrils alters central and peripheral immune cell profiles in non-transgenic mice (2019) · cites this paper as [9]
Activation of NF-kB can increase the release of proinflammatory cytokines TNF-α and IL-1β by microglial cells.
“The activation of this factor could increase the release of proinflammatory cytokines such TNF-α and interleukin 1β by microglial cells (Mogi et al., 1996; McLaughlin et al., 2006).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Mogi et al., 1996
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Carpenter, G., & Cohen, S. (1979) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.48.070179.001205 · Cited by 2,936 · see citing works
Van Snick, J. (1990) · Annual Review of Immunology · doi:10.1146/annurev.iy.08.040190.001345 · Cited by 1,890 · see citing works
Interleukin-1 regulates synthesis of nerve growth factor in non-neuronal cells of rat sciatic nerve
Lindholm, D., Heumann, R., Meyer, M., & Thoenen, H. (1987) · Nature · doi:10.1038/330658a0 · Cited by 994 · see citing works
Mogi, M., Harada, M., Riederer, P., Narabayashi, H., Fujita, K., & Nagatsu, T. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90746-3 · Cited by 986 · see citing works
Self-citationMogi, M., Harada, M., Kondo, T., Riederer, P., Inagaki, H., Minami, M., & Nagatsu, T. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90508-8 · Cited by 855 · see citing works
Self-citationTUMOR NECROSIS, CACHEXIA, SHOCK, AND INFLAMMATION: A COMMON MEDIATOR
Beutler, B., & Cerami, A. (1988) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.57.070188.002445 · Cited by 805 · see citing works
Ichinose, H., Ohye, T., Takahashi, E.-I., Seki, N., Hori, T.-A., Segawa, M., Nomura, Y., Endo, K., Tanaka, H., Tsuji, S., et al. (1994) · Nature Genetics · doi:10.1038/ng1194-236 · Cited by 770 · see citing works
Self-citationChung, I. Y., & Benveniste, E. N. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.144.8.2999 · Cited by 481 · see citing works
A comparison of clinical and pathological features of young‐ and old‐onset Parkinson's disease
Gibb, W. R. G., & Lees, A. J. (1988) · Neurology · doi:10.1212/wnl.38.9.1402 · Cited by 371 · see citing works
Trophic Stimulation of Cultured Neurons from Neonatal Rat Brain by Epidermal Growth Factor
Morrison, R. S., Kornblum, H. I., Leslie, F. M., & Bradshaw, R. A. (1987) · Science · doi:10.1126/science.3498986 · Cited by 294 · see citing works
Fibroblast growth factors stimulate nerve growth factor synthesis and secretion by astrocytes
Yoshida, K., & Gage, F. H. (1991) · Brain Research · doi:10.1016/0006-8993(91)90385-9 · Cited by 245 · see citing works
Mogi, M., Harada, M., Kondo, T., Narabayashi, H., Riederer, P. F., & Nagatsu, T. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11686-q · Cited by 166 · see citing works
Self-citationResearch Progress in Parkinson's Disease
Stern, G. M. (1981) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.44.7.656-a · Cited by 158 · see citing works
Biochemical neuropathology of Parkinson's disease.
Javoy-Agid, F., Ruberg, M., Taquet, H., Bokobza, B., Agid, Y., Gaspar, P., Berger, B., Nguyen-Legros, J., Alvarez, C., & Gray, F. (1984) · PubMed · Cited by 119 · see citing works
Juvenile parkinsonism--some clinical, pharmacological, and neuropathological aspects.
Yokochi, M., Narabayashi, H., Iizuka, R., & Nagatsu, T. (1984) · PubMed · Cited by 87 · see citing works
Self-citationKasahara, T., Yagisawa, H., Yamashita, K., et al. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)90657-9 · Cited by 63 · see citing works
Mogi, M., Kojima, K., & Nagatsu, T. (1984) · Analytical Biochemistry · doi:10.1016/0003-2697(84)90779-6 · Cited by 51 · see citing works
Self-citationCarvey, P. M., Ptak, L. R., Nath, S. T., et al. (1993) · Experimental Neurology · doi:10.1006/exnr.1993.1049 · Cited by 48 · see citing works
GTP cyclohydrolase I gene in hereditary progressive dystonia with marked diurnal fluctuation
Ichinose, H., Ohye, T., Segawa, M., et al. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11820-m · Cited by 48 · see citing works
Juvenile onset Parkinson's disease.
Gershanik, O. S., & Leist, A. (1987) · PubMed · Cited by 46 · see citing works
Research progress in Parkinson's disease
Rose, F. C., & Capildeo, R. (1981) · Medical Entomology and Zoology · Cited by 40 · see citing works
Katsuura, M., & Tanaka, S. (1989) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a122826 · Cited by 35 · see citing works
Martin, W. E., Resch, J. A., & BAKER, A. B. (1971) · Archives of Neurology · doi:10.1001/archneur.1971.00490060028003 · Cited by 30 · see citing works
Yu, S., Lo, E. S., Cochran, E. J., et al. (1994) · Experimental Neurology · doi:10.1006/exnr.1994.1038 · Cited by 25 · see citing works
Furukawa, Y., Kondo, T., Nishi, K., et al. (1991) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(91)90169-8 · Cited by 25 · see citing works
Snyder, S. H. (1991) · Nature · doi:10.1038/350195a0 · Cited by 24 · see citing works
Promising Protein for Parkinson's
Weiss, R. (1993) · Science · doi:10.1126/science.8493547 · Cited by 18 · see citing works
Johnson, G. D. (1989) · PubMed Central · Cited by 17 · see citing works
Inagaki, H., Katoh, M., Kurosawa-Ohsawa, K., & Tanaka, S. (1990) · Journal of Immunological Methods · doi:10.1016/0022-1759(90)90460-d · Cited by 15 · see citing works
Self-citationCell Death in Parkinson’s Disease
Pfeiffer, R. F., Wszolek, Z. K., & Ebadi, M. (2004) · CRC Press eBooks · doi:10.1201/9780203508596-52 · Cited by 14 · see citing works
GTP cyclohydrolase I activity in mononuclear blood cells in juvenile parkinsonism
Ichinose, H., Ohye, T., Yokochi, M., et al. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11511-t · Cited by 13 · see citing works
Perschak, H., Amsler, U., Vischer, A., et al. (1987) · PubMed · Cited by 10 · see citing works
Cell Death in Parkinson’s Disease
Smeyne, R. J., & Faherty, C. J. (2004) · CRC Press eBooks · doi:10.1201/9780203508596.ch42 · Cited by 8 · see citing works
(2010) · Springer eBooks · doi:10.1007/978-0-387-79948-3_4799 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Role of Oxidative Stress in Parkinson's Disease
Dias, V., Junn, E., & Mouradian, M. M. (2013) · Journal of Parkinson’s Disease · doi:10.3233/jpd-130230 · Cited by 1,845 · see citing works
-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446 · see citing works
Role of Pro-Inflammatory Cytokines Released from Microglia in Neurodegenerative Diseases
Smith, J. A., Das, A., Ray, S. K., & Banik, N. L. (2012) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2011.10.004 · Cited by 1,165 · see citing works
Tansey, M. G., & Goldberg, M. S. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.11.004 · Cited by 1,045 · see citing works
Colonic inflammation in Parkinson's disease
Devos, D., Lebouvier, T., Lardeux, B., Biraud, M., Rouaud, T., Pouclet, H., Coron, E., Bruley des Varannes, S., Naveilhan, P., Nguyen, J.-M., et al. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.09.007 · Cited by 627 · see citing works
Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy
Muzio, L., Viotti, A., & Martino, G. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.742065 · Cited by 581 · see citing works
The role of interleukin-1 in neuroinflammation and Alzheimer disease: an evolving perspective
Shaftel, S. S., Griffin, W. S. T., & O'Banion, M. K. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-7 · Cited by 565 · see citing works
Peripheral cytokines profile in parkinson’s disease
Reale, M., Iarlori, C., Thomas, A., Gambi, D., Perfetti, B., Di Nicola, M., & Onofrj, M. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.07.003 · Cited by 547 · see citing works
Role of TLR4 in the gut-brain axis in Parkinson's disease: A translational study from men to mice
Perez-Pardo, P., Dodiya, H. B., Engen, P. A., Forsyth, C. B., Huschens, A. M., Shaikh, M., Voigt, R. M., Naqib, A., Green, S. J., Kordower, J. H., et al. (2019) · Gut · doi:10.1136/gutjnl-2018-316844 · Cited by 467 · see citing works
Parkinson disease and the immune system - Associations, mechanisms and therapeutics
Tan, E.-K., Chao, Y.-X., West, A., Chan, L.-L., Poewe, W., & Jankovic, J. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0344-4 · Cited by 457 · see citing works
The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma.
Ramirez, A. I., de Hoz, R., Salobrar-Garcia, E., Salazar, J. J., Rojas, B., Ajoy, D., López-Cuenca, I., Rojas, P., Triviño, A., & Ramírez, J. M. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00214 · Cited by 466 · see citing works
Linking Neuroinflammation and Neurodegeneration in Parkinson's Disease
Gelders, G., Baekelandt, V., & Van der Perren, A. (2018) · Journal of Immunology Research · doi:10.1155/2018/4784268 · Cited by 430 · see citing works
Koprich, J. B., Reske-Nielsen, C., Mithal, P., & Isacson, O. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-8 · Cited by 355 · see citing works
Alterations of T-lymphocyte populations in Parkinson disease
Baba, Y., Kuroiwa, A., Uitti, R. J., Wszolek, Z. K., & Yamada, T. (2005) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2005.07.005 · Cited by 336 · see citing works
Toll-like receptors in the pathogenesis of neuroinflammation
Kumar, V. (2019) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2019.03.012 · Cited by 331 · see citing works
Brodacki, B., Staszewski, J., Toczyłowska, B., Kozłowska, E., Drela, N., Chalimoniuk, M., & Stępien, A. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.06.040 · Cited by 316 · see citing works
An inflammatory review of Parkinson's disease
Orr, C. F., Rowe, D. B., & Halliday, G. M. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00127-2 · Cited by 309 · see citing works
Microglial phenotypes in Parkinson’s disease and animal models of the disease
Joers, V., Tansey, M. G., Mulas, G., & Carta, A. R. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.04.006 · Cited by 285 · see citing works
Dzamko, N., Gysbers, A., Perera, G., Bahar, A., Shankar, A., Gao, J., Fu, Y., & Halliday, G. M. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1648-8 · Cited by 273 · see citing works
Wang, W., Nguyen, L. T. T., Burlak, C., Chegini, F., Guo, F., Chataway, T., Ju, S., Fisher, O. S., Miller, D. W., Datta, D., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1610099113 · Cited by 270 · see citing works
Sanchez-Guajardo, V., Febbraro, F., Kirik, D., & Romero-Ramos, M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008784 · Cited by 256 · see citing works
The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders
Morris, G., & Berk, M. (2015) · BMC Medicine · doi:10.1186/s12916-015-0310-y · Cited by 245 · see citing works
Sriram, K., Miller, D. B., & O'Callaghan, J. P. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03566.x · Cited by 242 · see citing works
Inflammation is genetically implicated in Parkinson’s disease
Dzamko, N., Geczy, C. L., & Halliday, G. M. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2014.10.028 · Cited by 222 · see citing works
Microglia affect α-synuclein cell-to-cell transfer in a mouse model of Parkinson’s disease
George, S., Rey, N. L., Tyson, T., Esquibel, C., Meyerdirk, L., Schulz, E., Pierce, S., Burmeister, A. R., Madaj, Z., Steiner, J. A., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0335-3 · Cited by 229 · see citing works
Tomás-Camardiel, M., Rite, I., Herrera, A. J., de Pablos, R. M., Cano, J., Machado, A., & Venero, J. L. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.01.010 · Cited by 203 · see citing works
The Role of LRRK2 in Neurodegeneration of Parkinson Disease
Rui, Q., Ni, H., Li, D., Gao, R., & Chen, G. (2018) · Current Neuropharmacology · doi:10.2174/1570159x16666180222165418 · Cited by 196 · see citing works
Chen, L.-L., Fan, Y.-G., Zhao, L.-X., Zhang, Q., & Wang, Z.-Y. (2023) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2022.106301 · Cited by 200 · see citing works
Immune Dysregulation in Autism Spectrum Disorder: What Do We Know about It?
Robinson-Agramonte, M. D. L. A., Noris García, E., Fraga Guerra, J., Vega Hurtado, Y., Antonucci, N., Semprún-Hernández, N., Schultz, S., & Siniscalco, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063033 · Cited by 176 · see citing works
Earls, R. H., Menees, K. B., Chung, J., Barber, J., Gutekunst, C.-A., Hazim, M. G., & Lee, J.-K. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1636-8 · Cited by 138 · see citing works
Deficient cortical development in the hydrocephalic texas (h-tx) rat: a role for CSF
Mashayekhi, F. (2002) · Brain · doi:10.1093/brain/awf182 · Cited by 115 · see citing works
The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive?
Doty, K. R., Guillot-Sestier, M.-V., & Town, T. (2015) · Brain Research · doi:10.1016/j.brainres.2014.09.008 · Cited by 104 · see citing works
Matousek, S. B., Ghosh, S., Shaftel, S. S., Kyrkanides, S., Olschowka, J. A., & O’Banion, M. K. (2012) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-011-9331-2 · Cited by 86 · see citing works
Peripheral Chemo-Cytokine Profiles in Alzheimers and Parkinsons Diseases
Reale, M., Greig, N., & Kamal, M. (2009) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/138955709789055199 · Cited by 82 · see citing works
Morais, L. H., Hara, D. B., Bicca, M. A., Poli, A., & Takahashi, R. N. (2018) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000389 · Cited by 58 · see citing works
(2020) · Advances in clinical chemistry · doi:10.1016/bs.acc.2019.07.012 · Cited by 46 · see citing works
Emerging Therapeutic Role of PPAR–α in Cognition and Emotions
Nisbett, K. E., & Pinna, G. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00998 · Cited by 37 · see citing works
RACF: A Multimodal Deep Learning Framework for Parkinson’s Disease Diagnosis Using SNP and MRI Data
Cao, J., & Long, X. (2025) · Applied Sciences · doi:10.3390/app15084513 · Cited by 22 · see citing works
Langston, J. W., Forno, L. S., Tetrud, J., Reeves, A. G., Kaplan, J. A., & Karluk, D. (1999) · Annals of Neurology · doi:10.1002/1531-8249(199910)46:4 · Cited by 1 · see citing works
- Authors
- Mogi, M., Harada, M., Narabayashi, H., Inagaki, H., Minami, M., & Nagatsu, T.
- Affiliations
- Matsumoto Dental University (JP)
- Juntendo University (JP)
- Nippon Medical School (JP)
- Fujita Health University (JP)
- Corresponding author
- Nagatsu, Toshiharu
- ORCID
- Nagatsu, Toshiharu
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 1996-06
- Volume
- 211
- Issue
- 1
- Pages
- 13-16
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W1997326200
- Cited by
- 545
- References
- 35
- Citations by year
- 2026: 8 · 2025: 20 · 2024: 28 · 2023: 29 · 2022: 30 · 2021: 28 · 2020: 28 · 2019: 23 · 2018: 28 · 2017: 26 · 2016: 22 · 2015: 16 · 2014: 30 · 2013: 18 · 2012: 22
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- IL-1β, interleukin-2, IL-4, interleukin-6, transforming growth factor-alpha, epidermal growth factor, ventricular cerebrospinal fluid, juvenile parkinsonism, Parkinson's disease, cytokines, neurodegeneration, dopaminergic neurons, neuroinflammation
- MeSH terms
- Adolescent, Adult, Aged, Cerebral Ventricles, Enzyme-Linked Immunosorbent Assay, Epidermal Growth Factor, Female, Humans, Interleukins, Male, Middle Aged, Mitogens, Nerve Degeneration, Parkinson Disease, Tumor Necrosis Factor-alpha, Transforming Growth Factor alpha, Age of Onset
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
