The role of the chemotactic cytokines in in tick-borne encephalitis – the observational clinical study

The role of the chemotactic cytokines in in tick-borne encephalitis – the observational clinical study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The role of the chemotactic cytokines in in tick-borne encephalitis – the observational clinical study Sambor Grygorczuk, Piotr Czupryna, Diana Martonik, Anna Parfieniuk-Kowerda, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4643861/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background In tick-borne encephalitis (TBE), central nervous system is infiltrated by a mixed leukocyte population detectable as cerebrospinal fluid (CSF) pleocytosis, contributing both to an infection control and immune-mediated pathology. The chemotactic pathways controlling this leukocyte influx are not well defined. Results We studied serum and CSF samples from 103 TBE patients, using normal serum (n=19) and CSF (n=12) as controls. We measured concentrations of the chemotactic cytokines IL-16, CXCL1, CXCL2, CXCL5, CXCL6, IL-8, CXCL9, CXCL10, CXCL11, CXCL13, CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL19, CCL20, CCL21, CX3CL1 and XCL1 with a micro-bead assay and of CXCL12 with ELISA. The CSF lymphocyte subpopulations were counted cytometrically with a fluorescent-labeled monoclonal antibody kit. DNA was isolated from patients’ blood samples and 10 polymorphisms in CCR2 , CCL5 , CCR5 , CXCR3 , CXCL10 , CXCL11 and CX3CR1 genes studied with real-time PCR. We analyzed results with non-parametric tests and created multivariate linear regression models of leukocyte population counts in CSF and of the clinical severity dependent on chemokine CSF levels. Except of CXCL2, CCL5 and XCL1, all the CSF chemokine concentrations were increased and the concentration index values favored their intrathecal synthesis. CXCL1, IL-8, CXCL10, CCL2, CCL3, CCL19 and CCL20 created chemotactic gradients towards CSF in 90-100% and CCL4, CCL7, CCL8 in about half of patients. The neutrophils associated predominantly with CXCL1 and IL-8 and the lymphocytes with IL-16, CCL19, CCL20, CCL4, CXCL12 and CXCL13, with consistent negative associations with CX 3 CL1 and CCL2. CCL11, CCL19, CXCL10 and CXCL13 associated with milder and CXCL1 and CCL20 with a more severe presentation. There were associations between the genotypes of CCR2, CCL5, CXCR3 and CX3CR1 and concentrations of the relevant chemokines. Conclusions CXCL1/CXCR2, IL-8/CXCR1, CCL19/CCR7, CCL20/CCR6, CCL4/CCR5, CXCL12/CXCR4, CXCL13/CXCR5 and possibly other signaling axes contribute to pleocytosis in TBE. IL-16 associates with pleocytosis in an unclear mechanism and CX 3 CL1 may be an antagonist of the leukocyte influx. The protective/immunopathogenic effects of chemokines are can be distinguished from their chemotactic effects, suggesting a complex relation between the inflammatory infiltrate and the clinical outcome. The genetic background influences chemokine expression in TBE. tick-borne encephalitis cerebrospinal fluid intrathecal immunity pleocytosis chemotaxis chemokines Full Text Additional Declarations No competing interests reported. Supplementary Files AdditionalFile1.tif AdditionalFile2.docx AdditionalFile3.docx AdditionalFile4.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4643861","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":323312562,"identity":"9881214b-fe6e-4b98-9f0d-73506dc1e420","order_by":0,"name":"Sambor 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study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"tick-borne encephalitis, cerebrospinal fluid, intrathecal immunity, pleocytosis, chemotaxis, chemokines","lastPublishedDoi":"10.21203/rs.3.rs-4643861/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4643861/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground\u003c/p\u003e\n\u003cp\u003eIn tick-borne encephalitis (TBE), central nervous system is infiltrated by a mixed leukocyte population detectable as cerebrospinal fluid (CSF) pleocytosis, contributing both to an infection control and immune-mediated pathology. The chemotactic pathways controlling this leukocyte influx are not well defined.\u003c/p\u003e\n\u003cp\u003eResults\u003c/p\u003e\n\u003cp\u003eWe studied serum and CSF samples from 103 TBE patients, using normal serum (n=19) and CSF (n=12) as controls. We measured concentrations of the chemotactic cytokines IL-16, CXCL1, CXCL2, CXCL5, CXCL6, IL-8, CXCL9, CXCL10, CXCL11, CXCL13, CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL19, CCL20, CCL21, CX3CL1 and XCL1 with a micro-bead assay and of CXCL12 with ELISA. The CSF lymphocyte subpopulations were counted cytometrically with a fluorescent-labeled monoclonal antibody kit. DNA was isolated from patients’ blood samples and 10 polymorphisms in \u003cem\u003eCCR2\u003c/em\u003e, \u003cem\u003eCCL5\u003c/em\u003e, \u003cem\u003eCCR5\u003c/em\u003e, \u003cem\u003eCXCR3\u003c/em\u003e, \u003cem\u003eCXCL10\u003c/em\u003e, \u003cem\u003eCXCL11\u003c/em\u003e and \u003cem\u003eCX3CR1\u003c/em\u003e genes studied with real-time PCR. We analyzed results with non-parametric tests and created multivariate linear regression models of leukocyte population counts in CSF and of the clinical severity dependent on chemokine CSF levels.\u003c/p\u003e\n\u003cp\u003eExcept of CXCL2, CCL5 and XCL1, all the CSF chemokine concentrations were increased and the concentration index values favored their intrathecal synthesis. CXCL1, IL-8, CXCL10, CCL2, CCL3, CCL19 and CCL20 created chemotactic gradients towards CSF in 90-100% and CCL4, CCL7, CCL8 in about half of patients. The neutrophils associated predominantly with CXCL1 and IL-8 and the lymphocytes with IL-16, CCL19, CCL20, CCL4, CXCL12 and CXCL13, with consistent negative associations with CX\u003csub\u003e3\u003c/sub\u003eCL1 and CCL2. CCL11, CCL19, CXCL10 and CXCL13 associated with milder and CXCL1 and CCL20 with a more severe presentation. There were associations between the genotypes of \u003cem\u003eCCR2, CCL5, CXCR3\u003c/em\u003e and \u003cem\u003eCX3CR1\u003c/em\u003e and concentrations of the relevant chemokines.\u003c/p\u003e\n\u003cp\u003eConclusions\u003c/p\u003e\n\u003cp\u003eCXCL1/CXCR2, IL-8/CXCR1, CCL19/CCR7, CCL20/CCR6, CCL4/CCR5, CXCL12/CXCR4, CXCL13/CXCR5 and possibly other signaling axes contribute to pleocytosis in TBE. IL-16 associates with pleocytosis in an unclear mechanism and CX\u003csub\u003e3\u003c/sub\u003eCL1 may be an antagonist of the leukocyte influx. The protective/immunopathogenic effects of chemokines are can be distinguished from their chemotactic effects, suggesting a complex relation between the inflammatory infiltrate and the clinical outcome. The genetic background influences chemokine expression in TBE.\u003c/p\u003e","manuscriptTitle":"The role of the chemotactic cytokines in in tick-borne encephalitis – the observational clinical study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-19 06:45:44","doi":"10.21203/rs.3.rs-4643861/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"be543648-1c86-49c9-8e3d-9d1c6ca9c81f","owner":[],"postedDate":"July 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-19T06:45:46+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-19 06:45:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4643861","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4643861","identity":"rs-4643861","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}