The intrathecal expression and pathogenetic role of Th17 cytokines and CXCR2-binding chemokines in tick-borne encephalitis
Abstract Background Tick-borne encephalitis (TBE) is a clinically variable but potentially severe Flavivirus infection, with the outcome strongly dependent on secondary immunopathology. Neutrophils are present in cerebrospinal fluid (CSF) of TBE patients, but their pathogenetic role remains unknown....
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-04-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-018-1138-0 |
| _version_ | 1811280323806232576 |
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| author | Sambor Grygorczuk Renata Świerzbińska Maciej Kondrusik Justyna Dunaj Piotr Czupryna Anna Moniuszko Agnieszka Siemieniako Sławomir Pancewicz |
| author_facet | Sambor Grygorczuk Renata Świerzbińska Maciej Kondrusik Justyna Dunaj Piotr Czupryna Anna Moniuszko Agnieszka Siemieniako Sławomir Pancewicz |
| author_sort | Sambor Grygorczuk |
| collection | DOAJ |
| description | Abstract Background Tick-borne encephalitis (TBE) is a clinically variable but potentially severe Flavivirus infection, with the outcome strongly dependent on secondary immunopathology. Neutrophils are present in cerebrospinal fluid (CSF) of TBE patients, but their pathogenetic role remains unknown. In animal models, neutrophils contributed both to the Flavivirus entry into central nervous system (CNS) and to the control of the encephalitis, which we attempted to evaluate in human TBE. Methods We analyzed records of 240 patients with TBE presenting as meningitis (n = 110), meningoencephalitis (n = 114) or meningoencephalomyelitis (n = 16) assessing CSF neutrophil count on admission and at follow-up 2 weeks later, and their associations with other laboratory and clinical parameters. We measured serum and CSF concentrations of Th17-type cytokines (interleukin-17A, IL-17F, IL-22) and chemokines attracting neutrophils (IL-8, CXCL1, CXCL2) in patients with TBE (n = 36 for IL-8, n = 15 for other), with non-TBE aseptic meningitis (n = 6) and in non-meningitis controls (n = 7), using commercial ELISA assays. The results were analyzed with non-parametric tests with p < 0.05 considered as significant. Results On admission, neutrophils were universally present in CSF constituting 25% (median) of total pleocytosis, but on follow-up, they were absent in most of patients (58%) and scarce (< 10%) in 36%. CSF neutrophil count did not correlate with lymphocyte count and blood-brain barrier integrity, did not differ between meningitis and meningoencephalitis, but was higher in meningoencephalomyelitis patients. Prolonged presence of neutrophils in follow-up CSF was associated with encephalitis and neurologic sequelae. All the studied cytokines were expressed intrathecally, with IL-8 having the highest CSF concentration index. Additionally, IL-17A concentration was significantly increased in serum. IL-17F and CXCL1 CSF concentrations correlated with neutrophil count and CXCL1 concentration was higher in patients with encephalitis. Conclusions The neutrophil CNS infiltrate does not correlate directly with TBE severity, but is associated with clinical features like myelitis, possibly being involved in its pathogenesis. Th17 cytokine response is present in TBE, especially intrathecally, and contributes to the CNS neutrophilic inflammation. IL-8 and CXCL1 may be chemokines directly responsible for the neutrophil migration. |
| first_indexed | 2024-04-13T01:11:33Z |
| format | Article |
| id | doaj.art-e1da5219021c499eb67a9f831a141772 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-13T01:11:33Z |
| publishDate | 2018-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-e1da5219021c499eb67a9f831a1417722022-12-22T03:09:08ZengBMCJournal of Neuroinflammation1742-20942018-04-0115112010.1186/s12974-018-1138-0The intrathecal expression and pathogenetic role of Th17 cytokines and CXCR2-binding chemokines in tick-borne encephalitisSambor Grygorczuk0Renata Świerzbińska1Maciej Kondrusik2Justyna Dunaj3Piotr Czupryna4Anna Moniuszko5Agnieszka Siemieniako6Sławomir Pancewicz7Department of the Infectious Disease and Neuroinfections, Medical University in BiałystokDepartment of the Infectious Disease and Neuroinfections, Medical University in BiałystokDepartment of the Infectious Disease and Neuroinfections, Medical University in BiałystokDepartment of the Infectious Disease and Neuroinfections, Medical University in BiałystokDepartment of the Infectious Disease and Neuroinfections, Medical University in BiałystokDepartment of the Infectious Disease and Neuroinfections, Medical University in BiałystokUniversity Hospital in BiałystokDepartment of the Infectious Disease and Neuroinfections, Medical University in BiałystokAbstract Background Tick-borne encephalitis (TBE) is a clinically variable but potentially severe Flavivirus infection, with the outcome strongly dependent on secondary immunopathology. Neutrophils are present in cerebrospinal fluid (CSF) of TBE patients, but their pathogenetic role remains unknown. In animal models, neutrophils contributed both to the Flavivirus entry into central nervous system (CNS) and to the control of the encephalitis, which we attempted to evaluate in human TBE. Methods We analyzed records of 240 patients with TBE presenting as meningitis (n = 110), meningoencephalitis (n = 114) or meningoencephalomyelitis (n = 16) assessing CSF neutrophil count on admission and at follow-up 2 weeks later, and their associations with other laboratory and clinical parameters. We measured serum and CSF concentrations of Th17-type cytokines (interleukin-17A, IL-17F, IL-22) and chemokines attracting neutrophils (IL-8, CXCL1, CXCL2) in patients with TBE (n = 36 for IL-8, n = 15 for other), with non-TBE aseptic meningitis (n = 6) and in non-meningitis controls (n = 7), using commercial ELISA assays. The results were analyzed with non-parametric tests with p < 0.05 considered as significant. Results On admission, neutrophils were universally present in CSF constituting 25% (median) of total pleocytosis, but on follow-up, they were absent in most of patients (58%) and scarce (< 10%) in 36%. CSF neutrophil count did not correlate with lymphocyte count and blood-brain barrier integrity, did not differ between meningitis and meningoencephalitis, but was higher in meningoencephalomyelitis patients. Prolonged presence of neutrophils in follow-up CSF was associated with encephalitis and neurologic sequelae. All the studied cytokines were expressed intrathecally, with IL-8 having the highest CSF concentration index. Additionally, IL-17A concentration was significantly increased in serum. IL-17F and CXCL1 CSF concentrations correlated with neutrophil count and CXCL1 concentration was higher in patients with encephalitis. Conclusions The neutrophil CNS infiltrate does not correlate directly with TBE severity, but is associated with clinical features like myelitis, possibly being involved in its pathogenesis. Th17 cytokine response is present in TBE, especially intrathecally, and contributes to the CNS neutrophilic inflammation. IL-8 and CXCL1 may be chemokines directly responsible for the neutrophil migration.http://link.springer.com/article/10.1186/s12974-018-1138-0Tick-borne encephalitisIntrathecal inflammationNeutrophilsTh17IL-22CXCL1 |
| spellingShingle | Sambor Grygorczuk Renata Świerzbińska Maciej Kondrusik Justyna Dunaj Piotr Czupryna Anna Moniuszko Agnieszka Siemieniako Sławomir Pancewicz The intrathecal expression and pathogenetic role of Th17 cytokines and CXCR2-binding chemokines in tick-borne encephalitis Journal of Neuroinflammation Tick-borne encephalitis Intrathecal inflammation Neutrophils Th17 IL-22 CXCL1 |
| title | The intrathecal expression and pathogenetic role of Th17 cytokines and CXCR2-binding chemokines in tick-borne encephalitis |
| title_full | The intrathecal expression and pathogenetic role of Th17 cytokines and CXCR2-binding chemokines in tick-borne encephalitis |
| title_fullStr | The intrathecal expression and pathogenetic role of Th17 cytokines and CXCR2-binding chemokines in tick-borne encephalitis |
| title_full_unstemmed | The intrathecal expression and pathogenetic role of Th17 cytokines and CXCR2-binding chemokines in tick-borne encephalitis |
| title_short | The intrathecal expression and pathogenetic role of Th17 cytokines and CXCR2-binding chemokines in tick-borne encephalitis |
| title_sort | intrathecal expression and pathogenetic role of th17 cytokines and cxcr2 binding chemokines in tick borne encephalitis |
| topic | Tick-borne encephalitis Intrathecal inflammation Neutrophils Th17 IL-22 CXCL1 |
| url | http://link.springer.com/article/10.1186/s12974-018-1138-0 |
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