{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T17:22:59Z","timestamp":1775064179610,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Hrvatska Zaklada za Znanost","doi-asserted-by":"publisher","award":["IP-2016-06-7456"],"award-info":[{"award-number":["IP-2016-06-7456"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Data on the immune response to West Nile virus (WNV) are limited. We analyzed the antiviral cytokine response in serum and cerebrospinal fluid (CSF) samples of patients with WNV fever and WNV neuroinvasive disease using a multiplex bead-based assay for the simultaneous quantification of 13 human cytokines. The panel included cytokines associated with innate and early pro-inflammatory immune responses (TNF-\u03b1\/IL-6), Th1 (IL-2\/IFN-\u03b3), Th2 (IL-4\/IL-5\/IL-9\/IL-13), Th17 immune response (IL-17A\/IL-17F\/IL-21\/IL-22) and the key anti-inflammatory cytokine IL-10. Elevated levels of IFN-\u03b3 were detected in 71.7% of CSF and 22.7% of serum samples (p = 0.003). Expression of IL-2\/IL-4\/TNF-\u03b1 and Th1 17 cytokines (IL-17A\/IL-17F\/IL-21) was detected in the serum but not in the CSF (except one positive CSF sample for IL-17F\/IL-4). While IL-6 levels were markedly higher in the CSF compared to serum (CSF median 2036.71, IQR 213.82\u20136190.50; serum median 24.48, IQR 11.93\u201349.81; p &lt; 0.001), no difference in the IL-13\/IL-9\/IL-10\/IFN-\u03b3\/IL-22 levels in serum\/CSF was found. In conclusion, increased concentrations of the key cytokines associated with innate and early acute phase responses (IL-6) and Th1 type immune responses (IFN-\u03b3) were found in the CNS of patients with WNV infection. In contrast, expression of the key T-cell growth factor IL-2, Th17 cytokines, a Th2 cytokine IL-4 and the proinflammatory cytokine TNF-\u03b1 appear to be concentrated mainly in the periphery.<\/jats:p>","DOI":"10.3390\/v13020342","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T20:42:51Z","timestamp":1614026571000},"page":"342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Antiviral Cytokine Response in Neuroinvasive and Non-Neuroinvasive West Nile Virus Infection"],"prefix":"10.3390","volume":"13","author":[{"given":"Snjezana","family":"Zidovec-Lepej","sequence":"first","affiliation":[{"name":"Department of Immunological and Molecular Diagnostics, University Hospital for Infectious Diseases \u201cDr Fran Mihaljevic\u201d, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1877-5547","authenticated-orcid":false,"given":"Tatjana","family":"Vilibic-Cavlek","sequence":"additional","affiliation":[{"name":"Department of Virology, Croatian Institute of Public Health,10000 Zagreb, Croatia"},{"name":"Department of Microbiology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ljubo","family":"Barbic","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Ilic","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Croatian Institute of Public Health, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0398-5346","authenticated-orcid":false,"given":"Vladimir","family":"Savic","sequence":"additional","affiliation":[{"name":"Laboratory for Virology and Serology, Poultry Center, Croatian Veterinary Institute, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irena","family":"Tabain","sequence":"additional","affiliation":[{"name":"Department of Virology, Croatian Institute of Public Health,10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4917-9270","authenticated-orcid":false,"given":"Thomas","family":"Ferenc","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Reanimatology and Intensive Care Medicine, Merkur University Hospital, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Grgic","sequence":"additional","affiliation":[{"name":"Department of Immunological and Molecular Diagnostics, University Hospital for Infectious Diseases \u201cDr Fran Mihaljevic\u201d, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lana","family":"Gorenec","sequence":"additional","affiliation":[{"name":"Department of Immunological and Molecular Diagnostics, University Hospital for Infectious Diseases \u201cDr Fran Mihaljevic\u201d, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Bogdanic","sequence":"additional","affiliation":[{"name":"Department of Virology, Croatian Institute of Public Health,10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9572-8760","authenticated-orcid":false,"given":"Vladimir","family":"Stevanovic","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario","family":"Sabadi","sequence":"additional","affiliation":[{"name":"Clinic for Infectious Diseases, Clinical Hospital Center Osijek, 31000 Osijek, Croatia"},{"name":"Medical Faculty, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ljiljana","family":"Peric","sequence":"additional","affiliation":[{"name":"Clinic for Infectious Diseases, Clinical Hospital Center Osijek, 31000 Osijek, Croatia"},{"name":"Medical Faculty, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja","family":"Potocnik-Hunjadi","sequence":"additional","affiliation":[{"name":"Clinic for Infectious Diseases, County Hospital Cakovec, 40000 Cakovec, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeta","family":"Dvorski","sequence":"additional","affiliation":[{"name":"Clinic for Infectious Diseases, General Hospital Varazdin, 42000 Varazdin, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Butigan","sequence":"additional","affiliation":[{"name":"Clinic for Infectious Diseases, General Hospital Varazdin, 42000 Varazdin, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krunoslav","family":"Capak","sequence":"additional","affiliation":[{"name":"Environmental Health Department, Croatian Institute of Public Health, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eddy","family":"Listes","sequence":"additional","affiliation":[{"name":"Laboratory for Diagnostics, Croatian Veterinary Institute, Veterinary Institute Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Savini","sequence":"additional","affiliation":[{"name":"Department of Virology, OIE Reference Center for West Nile Disease, Istituto Zooprofilattico Sperimentale \u201cG. Caporale\u201d, 64100 Teramo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"key":"ref_1","unstructured":"Clark, M.B., and Schaefer, T.J. (2020). West Nile Virus, StatPearls Publishing."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"606","DOI":"10.3390\/v6020606","article-title":"Clinical Manifestations and Outcomes of West Nile Virus Infection","volume":"6","author":"Sejvar","year":"2014","journal-title":"Viruses"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1097\/INF.0b013e3180cc2c3f","article-title":"West Nile Virus Cerebellitis in a Healthy 10-Year-Old Child","volume":"26","author":"Natarajan","year":"2007","journal-title":"Pediatr. Infect. Dis. 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