{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:06:13Z","timestamp":1792789573527,"version":"4.5.0"},"reference-count":36,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"internal grant","award":["MB\/M\/09[16]"],"award-info":[{"award-number":["MB\/M\/09[16]"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Progressive supranuclear palsy (PSP) is an atypical parkinsonian syndrome based on tau pathology; its clinical phenotype differs, but PSP with Richardson\u2019s syndrome (PSP-RS) and the PSP parkinsonism predominant (PSP-P) variant remain the two most common manifestations. Neuroinflammation is involved in the course of the disease and may cause neurodegeneration. However, an up-to-date cytokine profile has not been assessed in different PSP phenotypes. This study aimed to evaluate possible differences in neuroinflammatory patterns between the two most common PSP phenotypes. Serum and cerebrospinal fluid (CSF) concentrations of interleukin-1 beta (IL-1\u03b2) and IL-6 were analyzed using enzyme-linked immunosorbent assay (ELISA) kits in 36 study participants\u201412 healthy controls and 24 patients with a clinical diagnosis of PSP-12 PSP-RS and 12 PSP-P. Disease duration among PSP patients ranged from three to six years. All participants underwent basic biochemical testing, and neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values were calculated. Due to a lack of neuropathological examinations, as all patients remain alive, total tau levels were assessed in the CSF. Tau levels were significantly higher in the PSP-P and PSP-RS groups compared to the healthy controls. The lowest concentrations of serum and CSF interleukins were observed in PSP-RS patients, whereas PSP-P patients and healthy controls had significantly higher interleukin concentrations. Furthermore, there was a significant correlation between serum IL-6 levels and PLR in PSP-RS patients. The results indicate the existence of distinct neuroinflammatory patterns or a neuroprotective role of increased inflammatory activity, which could cause the differences between PSPS phenotypes and clinical course. The causality of the correlations described requires further studies to be confirmed.<\/jats:p>","DOI":"10.3390\/ijms242015135","type":"journal-article","created":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T06:07:26Z","timestamp":1697177246000},"page":"15135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Clinical Phenotypes of Progressive Supranuclear Palsy\u2014The Differences in Interleukin Patterns"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8685-475X","authenticated-orcid":false,"given":"Natalia","family":"Madetko-Alster","sequence":"first","affiliation":[{"name":"Department of Neurology, Medical University of Warsaw, Kondratowicza 8, 03-242 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmara","family":"Otto-\u015alusarczyk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Wierci\u0144ska-Drapa\u0142o","sequence":"additional","affiliation":[{"name":"Department of Infectious and Tropical Diseases and Hepatology, Medical University of Warsaw, Wolska 37, 01-201 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariusz","family":"Koziorowski","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Warsaw, Kondratowicza 8, 03-242 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4188-5901","authenticated-orcid":false,"given":"Stanis\u0142aw","family":"Szlufik","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Warsaw, Kondratowicza 8, 03-242 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Samborska-\u0106wik","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Warsaw, Kondratowicza 8, 03-242 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0181-3607","authenticated-orcid":false,"given":"Marta","family":"Struga","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Warsaw, Kondratowicza 8, 03-242 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5371-6817","authenticated-orcid":false,"given":"Piotr","family":"Alster","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Warsaw, Kondratowicza 8, 03-242 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1002\/mds.26987","article-title":"Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria","volume":"32","author":"Respondek","year":"2017","journal-title":"Mov. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3389\/fneur.2020.00180","article-title":"Progressive Supranuclear Palsy-Parkinsonism Predominant (PSP-P)-A Clinical Challenge at the Boundaries of PSP and Parkinson\u2019s Disease (PD)","volume":"11","author":"Alster","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0304-3940(92)90145-W","article-title":"Appearance of paired nucleated, Tau-positive glia in patients with progressive supranuclear palsy brain tissue","volume":"135","author":"Yamada","year":"1992","journal-title":"Neurosci. Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"893","DOI":"10.3389\/fnins.2020.00893","article-title":"Microglial Activation and Inflammation as a Factor in the Pathogenesis of Progressive Supranuclear Palsy (PSP)","volume":"14","author":"Alster","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1007\/s00221-017-4978-4","article-title":"Cathepsin S increases tau oligomer formation through limited cleavage, but only IL-6, not cathepsin S serum levels correlate with disease severity in the neurodegenerative tauopathy progressive supranuclear palsy","volume":"235","author":"Schuberth","year":"2017","journal-title":"Exp. Brain Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1212\/WNL.46.4.922","article-title":"Accuracy of clinical criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome)","volume":"46","author":"Litvan","year":"1996","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7781","DOI":"10.1038\/s41598-019-44234-y","article-title":"Increased prefrontal cortex interleukin-2 protein levels and shift in the peripheral T cell population in progressive supranuclear palsy patients","volume":"9","author":"Rydbirk","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_8","first-page":"5","article-title":"Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill","volume":"102","author":"Zahorec","year":"2001","journal-title":"Bratisl. Lek. Listy."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hosseini, S., Shafiabadi, N., Khanzadeh, M., Ghaedi, A., Ghorbanzadeh, R., Azarhomayoun, A., Bazrgar, A., Pezeshki, J., Bazrafshan, H., and Khanzadeh, S. (2023). Neutrophil to lymphocyte ratio in Parkinson\u2019s disease: A systematic review and meta-analysis. BMC Neurol., 23.","DOI":"10.1186\/s12883-023-03380-7"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e3261","DOI":"10.1002\/brb3.3261","article-title":"Neutrophil-to-lymphocyte ratio is associated with stroke progression and functional outcome in patients with ischemic stroke","volume":"24","author":"Xu","year":"2023","journal-title":"Brain Behav."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15347346231197884","DOI":"10.1177\/15347346231197884","article-title":"Association of Monocyte to Lymphocyte, Neutrophil to Lymphocyte, and Platelet to Lymphocyte Ratios with Non-Healing Lower Extremity Ulcers in Patients with Type 2 Diabetes","volume":"13","author":"Gao","year":"2023","journal-title":"Int. J. Low Extrem. Wounds"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1007\/s00268-011-0984-z","article-title":"Preoperative neutrophil-to-lymphocyte ratio (NLR) is associated with reduced disease-free survival following curative resection of pancreatic adenocarcinoma","volume":"35","author":"Garcea","year":"2011","journal-title":"World J. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1007\/s10072-019-04208-4","article-title":"The neutrophil-to-lymphocyte ratio as a marker of peripheral inflammation in progressive supranuclear palsy: A retrospective study","volume":"41","author":"Inci","year":"2020","journal-title":"Neurol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"97","DOI":"10.5603\/PJNNS.a2020.0097","article-title":"Neutrophil-to-lymphocyte ratio (NLR) at boundaries of Progressive Supranuclear Palsy Syndrome (PSPS) and Corticobasal Syndrome (CBS)","volume":"55","author":"Alster","year":"2021","journal-title":"Neurol. Neurochir. Polska"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"148","DOI":"10.5603\/PJNNS.a2022.0014","article-title":"Platelet-to-lymphocyte ratio and neutrophil-tolymphocyte ratio may reflect differences in PD and MSA-P neuroinflammation patterns","volume":"56","author":"Madetko","year":"2022","journal-title":"Neurol. Neurochir. Polska"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1186\/s12974-018-1339-6","article-title":"Cerebrospinal fluid pro-inflammatory cytokines differentiate parkinsonian syndromes","volume":"15","author":"Starhof","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13276","DOI":"10.1038\/s41598-018-31517-z","article-title":"Cerebrospinal fluid concentrations of inflammatory markers in Parkinson\u2019s disease and atypical parkinsonian disorders","volume":"8","author":"Hall","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rauf, A., Badoni, H., Abu-Izneid, T., Olatunde, A., Rahman, M.M., Painuli, S., Semwal, P., Wilairatana, P., and Mubarak, M.S. (2022). Neuroinflammatory Markers: Key Indicators in the Pathology of Neurodegenerative Diseases. Molecules, 27.","DOI":"10.3390\/molecules27103194"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/imm.13462","article-title":"The roles of interleukin-1 receptor accessory protein in certain inflammatory conditions","volume":"166","author":"Aghamohamadi","year":"2022","journal-title":"Immunology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1002\/alz.12341","article-title":"Acute systemic inflammation exacerbates neuroinflammation in Alzheimer\u2019s disease: IL-1\u03b2 drives amplified responses in primed astrocytes and neuronal network dysfunction","volume":"17","author":"Hennessy","year":"2021","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12974-023-02747-4","article-title":"IL-1\u03b2 and TNF-\u03b1 play an important role in modulating the risk of periodontitis and Alzheimer\u2019s disease","volume":"20","author":"Wang","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1016\/j.bbamcr.2016.03.018","article-title":"The role of interleukin-6 signaling in nervous tissue","volume":"1863","author":"Rothaug","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e200095","DOI":"10.1212\/NXI.0000000000200095","article-title":"Levels of Soluble Interleukin 6 Receptor and Asp358Ala Are Associated with Cognitive Performance and Alzheimer Disease Biomarkers","volume":"10","author":"Quillen","year":"2023","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13195-022-01118-0","article-title":"Serum IL-6, sAXL, and YKL-40 as systemic correlates of reduced brain structure and function in Alzheimer\u2019s disease: Results from the DELCODE study","volume":"15","author":"Brosseron","year":"2023","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/S0197-4580(01)00287-1","article-title":"Interleukin-1, neuroinflammation, and Alzheimer\u2019s disease","volume":"22","author":"Mrak","year":"2001","journal-title":"Neurobiol. Aging"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1093\/jnen\/59.6.471","article-title":"Interleukin-1 and the immunogenetics of Alzheimer\u2019s disease","volume":"59","author":"Mrak","year":"2000","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1189\/jlb.72.2.233","article-title":"Interleukin-1 in the genesis and progression of and risk for development of neuronal degeneration in Alzheimer\u2019s disease","volume":"72","author":"Griffin","year":"2002","journal-title":"J. Leukoc. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1136\/jnnp.2003.019422","article-title":"Increased intrathecal inflammatory activity in frontotemporal dementia: Pathophysiological implications","volume":"75","author":"Folkesson","year":"2004","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s12974-019-1505-5","article-title":"Reactive microglia and IL1\u03b2\/IL-1R1-signaling mediate neuroprotection in excitotoxin-damaged mouse retina","volume":"16","author":"Todd","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.cell.2020.02.013","article-title":"Repopulating Microglia Promote Brain Repair in an IL-6-Dependent Manner","volume":"180","author":"Willis","year":"2020","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"40065","DOI":"10.18632\/oncotarget.16990","article-title":"Neuroprotection by IFN-\u03b3 via astrocyte-secreted IL-6 in acute neuroinflammation","volume":"8","author":"Sun","year":"2017","journal-title":"Oncotarget"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1186\/1742-2094-10-59","article-title":"Acute and subacute IL-1\u03b2 administrations differentially modulate neuroimmune and neurotrophic systems: Possible implications for neuroprotection and neurodegeneration","volume":"10","author":"Song","year":"2013","journal-title":"J. Neuroinflamm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.parkreldis.2020.01.019","article-title":"Magnetic Resonance Parkinsonism Index for evaluating disease progression rate in progressive supranuclear palsy: A longitudinal 2-year study","volume":"72","author":"Quattrone","year":"2020","journal-title":"Park. Relat. Disord."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.parkreldis.2018.07.016","article-title":"A new MR imaging index for differentiation of progressive supranuclear palsy-parkinsonism from Parkinson\u2019s disease","volume":"54","author":"Quattrone","year":"2018","journal-title":"Park. Relat. Disord."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1159\/000121388","article-title":"Different tau pathology pattern in two clinical phenotypes of progressive supranuclear palsy","volume":"5","author":"Jellinger","year":"2008","journal-title":"Neurodegener. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/mdc3.12473","article-title":"Role of corpus callosum volumetry in differentiating the subtypes of progressive supranuclear palsy and early Parkinson\u2019s disease","volume":"4","author":"Lenka","year":"2017","journal-title":"Mov. Disord. Clin. Pract."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/20\/15135\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:06:06Z","timestamp":1760130366000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/20\/15135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,13]]},"references-count":36,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["ijms242015135"],"URL":"https:\/\/doi.org\/10.3390\/ijms242015135","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,13]]}}}