title: Increased levels of sphingosine-1-phosphate in cerebrospinal fluid of patients diagnosed with tick-borne encephalitis.
abstract: BACKGROUND
  Tick-borne encephalitis (TBE) is a serious acute central nervous system infection that can result in death or long-term neurological dysfunctions. We hypothesize that changes in sphingosine-1-phosphate (S1P) concentration occur during TBE development.
  
  
  METHODS
  S1P and interleukin-6 (IL-6) concentrations in blood plasma and cerebrospinal fluid (CSF) were measured using HPLC and ELISA, respectively. The effects of S1P on cytoskeletal structure and IL-6 production were assessed using rat astrocyte primary cultures with and without addition of plasma gelsolin and the S1P receptor antagonist fingolimod phosphate (FTY720P).
  
  
  RESULTS
  We report that acute inflammation due to TBE virus infection is associated with elevated levels of S1P and IL-6 in the CSF of infected patients. This elevated concentration is observed even at the earliest neurologic stage of disease, and may be controlled by glucocorticosteroid anti-inflammatory treatment, administered to patients unresponsive to antipyretic drugs and who suffer from a fever above 39°C. In vitro, treatment of confluent rat astrocyte monolayers with a high concentration of S1P (5 μM) results in cytoskeletal actin remodeling that can be prevented by the addition of recombinant plasma gelsolin, FTY720P, or their combination. Additionally, gelsolin and FTY720P significantly decreased S1P-induced release of IL-6.
  
  
  CONCLUSIONS
  TBE is associated with increased concentration of S1P and IL-6 in CSF, and this increase might promote development of inflammation. The consequences of increased extracellular S1P can be modulated by gelsolin and FTY720P. Therefore, blocking the inflammatory response at sites of infection by agents modulating S1P pathways might aid in developing new strategies for TBE treatment.
authors.forename: Alina
authors.initials: A
authors.lastname: Kułakowska
authors.forename: Fitzroy J
authors.initials: FJ
authors.lastname: Byfield
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zendzian-Piotrowska
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Zajkowska
authors.forename: Wiesław
authors.initials: W
authors.lastname: Drozdowski
authors.forename: Barbara
authors.initials: B
authors.lastname: Mroczko
authors.forename: Paul A
authors.initials: PA
authors.lastname: Janmey
authors.forename: Robert
authors.initials: R
authors.lastname: Bucki
mesh_terms: D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002851:Chromatography, High Pressure Liquid; D004675:Encephalitis, Tick-Borne / Q000134:cerebrospinal fluid* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D008246:Lysophospholipids / Q000134:cerebrospinal fluid* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D051381:Rats; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine