{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T14:22:51Z","timestamp":1785248571213,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T00:00:00Z","timestamp":1667001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Croatian Science Foundatio","award":["IP-2016-06-7456"],"award-info":[{"award-number":["IP-2016-06-7456"]}]},{"name":"Croatian Science Foundatio","award":["10106-22-3053"],"award-info":[{"award-number":["10106-22-3053"]}]},{"name":"Croatian Science Foundatio","award":["653316"],"award-info":[{"award-number":["653316"]}]},{"name":"School of Medicine, University of Zagreb","award":["IP-2016-06-7456"],"award-info":[{"award-number":["IP-2016-06-7456"]}]},{"name":"School of Medicine, University of Zagreb","award":["10106-22-3053"],"award-info":[{"award-number":["10106-22-3053"]}]},{"name":"School of Medicine, University of Zagreb","award":["653316"],"award-info":[{"award-number":["653316"]}]},{"name":"European Virus Archive goes Global (EVAg) project","award":["IP-2016-06-7456"],"award-info":[{"award-number":["IP-2016-06-7456"]}]},{"name":"European Virus Archive goes Global (EVAg) project","award":["10106-22-3053"],"award-info":[{"award-number":["10106-22-3053"]}]},{"name":"European Virus Archive goes Global (EVAg) project","award":["653316"],"award-info":[{"award-number":["653316"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Tick-borne encephalitis virus (TBEV) is one of the most significant arboviruses affecting the human central nervous system (CNS) in Europe. Data on cytokine response in TBEV infection are limited. Methods: We analyzed the cytokine response in serum, cerebrospinal fluid (CSF) and urine samples of patients with TBE. The control group consisted of patients with \u2018febrile headache\u2019 who had normal CSF cytology. The panel included 12 cytokines: TNF-\u03b1, IL-6, Th1 (IL-2, IFN-\u03b3), Th2 (IL-4, IL-5, IL-13), Th9 (IL-9), Th17 (IL-17A, IL-17F), Th22 (IL-22) cytokines and IL-10. Results: TBE patients were more likely to have increased levels of IL-6 and IFN-\u03b3 in CSF compared to controls (85.7% vs. 58.8% and 85.7% vs. 47.1%, respectively). However, concentrations of IL-6 (the most abundant cytokine in the CSF of both groups), IL-10 and IL-9 were lower in TBEV patients compared with controls, but the difference was statistically significant for IL-9 only (p = 0.001). By analyzing the cytokine levels in different clinical samples, all measured cytokines were detected in the serum, with the highest concentrations found for IFN-\u03b3, TNF-\u03b1, IL-10, IL-17F and IL-22. Higher concentrations of cytokines in the CSF compared with serum were observed for IL-5, IL-6 and IL-22. All cytokines except IL-13 were detectable in urine but in a small proportion of patients, except for IL-22, which was detectable in 95.8% of patients. Conclusions: Cytokine composition in different clinical samples of TBE patients reveals a different network of early innate immune response cytokines, Th1, Th2, Th9, Th22, Th17 and anti-inflammatory cytokines.<\/jats:p>","DOI":"10.3390\/vaccines10111825","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T10:47:57Z","timestamp":1667126877000},"page":"1825","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Quantification of Antiviral Cytokines in Serum, Cerebrospinal Fluid and Urine of Patients with Tick-Borne Encephalitis in Croatia"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9852-5806","authenticated-orcid":false,"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Ilic","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Croatian Institute of Public Health, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Bogdanic","sequence":"additional","affiliation":[{"name":"Department of Virology, Croatian Institute of Public Health,10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9362-7213","authenticated-orcid":false,"given":"Leona","family":"Radmanic","sequence":"additional","affiliation":[{"name":"Department of Immunological and Molecular Diagnostics, University Hospital for Infectious Diseases \u201cDr Fran Mihaljevic\u201d, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4917-9270","authenticated-orcid":false,"given":"Thomas","family":"Ferenc","sequence":"additional","affiliation":[{"name":"Clinical Department of Diagnostic and Interventional Radiology, Merkur University Hospital, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9078-1773","authenticated-orcid":false,"given":"Zeljka","family":"Hruskar","sequence":"additional","affiliation":[{"name":"Department of Virology, Croatian Institute of Public Health,10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0208-5821","authenticated-orcid":false,"given":"Luka","family":"Svitek","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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ljiljana","family":"Peric","sequence":"additional","affiliation":[{"name":"Medical Faculty, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dubravka","family":"Lisnjic","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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0706-961X","authenticated-orcid":false,"given":"Danijela","family":"Lakoseljac","sequence":"additional","affiliation":[{"name":"Primorje-Gorski Kotar County Teaching Institute of Public Health, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8599-8951","authenticated-orcid":false,"given":"Dobrica","family":"Roncevic","sequence":"additional","affiliation":[{"name":"Primorje-Gorski Kotar County Teaching Institute of Public Health, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5170-947X","authenticated-orcid":false,"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":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.antiviral.2019.01.014","article-title":"Tick-borne encephalitis in Europe and Russia: Review of pathogenesis, 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