{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T16:43:18Z","timestamp":1776184998143,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,27]],"date-time":"2025-04-27T00:00:00Z","timestamp":1745712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bulgarian Ministry of Education and Science (MES) under the Bulgarian National Recovery and Resilience Plan, Component \u201cInnovative Bulgaria\u201d","award":["BG-RRP-2.004-0006-C02"],"award-info":[{"award-number":["BG-RRP-2.004-0006-C02"]}]},{"name":"Bulgarian Ministry of Education and Science (MES) under the Bulgarian National Recovery and Resilience Plan, Component \u201cInnovative Bulgaria\u201d","award":["\u2116 2\/2021"],"award-info":[{"award-number":["\u2116 2\/2021"]}]},{"name":"Medical Faculty, Trakia University, Stara Zagora, Bulgaria","award":["BG-RRP-2.004-0006-C02"],"award-info":[{"award-number":["BG-RRP-2.004-0006-C02"]}]},{"name":"Medical Faculty, Trakia University, Stara Zagora, Bulgaria","award":["\u2116 2\/2021"],"award-info":[{"award-number":["\u2116 2\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Respiratory syncytial virus (RSV) and rhinovirus (RV)\u2014the two primary causative viruses of bronchiolitis in children\u2014have been studied extensively in terms of their associations with disease severity and serious late disease outcomes. In this study, we explored the differences in the clinical values of IFN-\u03b3 and IL-10 serum levels in RSV and RV bronchiolitis in the Bulgarian childhood population. Eighty-eight children with acute bronchiolitis, aged two months to two years, who were admitted to the General Pediatrics Clinic of University Hospital \u201cProf. St. Kirkovich\u201d, Stara Zagora, Bulgaria served as this study\u2019s subjects. The degree of wheezing and respiratory failure were classified. Naso-pharyngeal swabs were collected from all participants, and molecular identification of viruses was performed using real-time PCR. Serum samples were used to determine IFN-\u03b3 and IL-10 quantities using ELISA kits, and data are presented as the median IQR (25\u201375%). The total serum IL-10 levels were significantly enhanced in RSV-infected children compared to those infected with RV (14.4 (12.2\u201324.0) vs. 8.9 (7.2\u201312.5); p &lt; 0.001) and the other viral bronchiolitis groups (14.4 (12.2\u201324.0) vs. 6.65 (3.9\u201315.3); p = 0.003). The highest IL-10 levels (14.4 (12.8\u201327.9)) were found in RSV-positive patients with first-degree respiratory failure. Almost identical serum IFN-\u03b3 levels were determined for RSV- and RV-positive bronchiolitis patients (3.2 (1.6\u20136.8) and 2.8 (1.1\u20137.3); p = 0.781). Variance analysis of IL-10 serum levels revealed statistically significant differences among the patient groups depending on the type of viral infection, concerning respiratory failure (p = 0.005) and wheezing severity (p = 0.017). Our findings show that the IL-10 levels and the type of virus have a combined effect on disease severity. These data might contribute to patients\u2019 personalized\/individualized therapy and the prevention of recurrent wheezing later in life.<\/jats:p>","DOI":"10.3390\/pathogens14050426","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T07:49:36Z","timestamp":1745912976000},"page":"426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Systemic IL-10 and IFN-\u03b3 Levels in Respiratory Syncytial Virus- and Rhinovirus-Infected Bulgarian Children with Acute Bronchiolitis and Their Impact on Clinical Manifestation"],"prefix":"10.3390","volume":"14","author":[{"given":"Emiliya","family":"Kostadinova","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Medical Faculty, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9119-6373","authenticated-orcid":false,"given":"Svetla","family":"Angelova","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology, Microbiology, Parasitology and Infectious Diseases, Medical Faculty, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsvetana","family":"Tsonkova-Popova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical Faculty, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dima","family":"Zlateva","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical Faculty, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rozalina","family":"Yordanova","sequence":"additional","affiliation":[{"name":"Department of Health Care, Medical College, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1368-9081","authenticated-orcid":false,"given":"Spaska","family":"Stanilova","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1056\/NEJMra1413456","article-title":"Viral Bronchiolitis in Children","volume":"374","author":"Meissner","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0140-6736(16)30951-5","article-title":"Viral bronchiolitis","volume":"389","author":"Florin","year":"2017","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/j.1651-2227.2008.01023.x","article-title":"Multiple viral respiratory pathogens in children with bronchiolitis","volume":"98","author":"Stempel","year":"2008","journal-title":"Acta Paediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1111\/pai.12318","article-title":"The first wheezing episode: Respiratory virus etiology, atopic characteristics, and illness severity","volume":"25","author":"Turunen","year":"2014","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1757-7241-22-23","article-title":"Acute bronchiolitis in infants, a review","volume":"22","author":"Skjerven","year":"2014","journal-title":"Scand. J. Trauma. Resusc. Emerg. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kenmoe, S., Kengne-Nde, C., Ebogo-Belobo, J.T., Mbaga, D.S., Modiyinji, A.F., and Njouom, R. (2020). Systematic review and meta-analysis of the prevalence of common respiratory viruses in children <2 years with bronchiolitis in the pre-COVID-19 pandemic era. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0242302"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jpeds.2021.03.036","article-title":"Respiratory Virus Surveillance in Infants across Different Clinical Settings","volume":"234","author":"Haddadin","year":"2021","journal-title":"J. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1007\/s00431-018-3138-6","article-title":"Characteristics of children admitted to intensive care with acute bronchiolitis","volume":"177","author":"Ghazaly","year":"2018","journal-title":"Eur. J. Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/ppul.21552","article-title":"Infection with multiple viruses is not associated with increased disease severity in children with bronchiolitis","volume":"47","author":"Brand","year":"2012","journal-title":"Pediatr. Pulmonol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1007\/s00431-014-2334-2","article-title":"Virologic testing in bronchiolitis: Does it change management decisions and predict outcomes?","volume":"173","author":"Stollar","year":"2014","journal-title":"Eur. J. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1080\/20477724.2017.1375708","article-title":"Prevalence and genetic characterisation of respiratory syncytial viruses circulating in Bulgaria during the 2014\/15 and 2015\/16 winter seasons","volume":"111","author":"Korsun","year":"2017","journal-title":"Pathog. Glob. Health."},{"key":"ref_12","first-page":"219","article-title":"Prevalence of the respiratory syncytial virus infection in the winter and spring months among Bulgarian children younger than 2 years of age","volume":"3","author":"Kostadinova","year":"2024","journal-title":"Trakia J. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/all.13624","article-title":"Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments","volume":"74","author":"Jartti","year":"2019","journal-title":"Allergy Eur. J. Allergy Clin. Immunol."},{"key":"ref_14","first-page":"4","article-title":"New paradigms in acute viral bronchiolitis: Is it time to change our approach?","volume":"10","author":"Astudillo","year":"2024","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1080\/17476348.2016.1190647","article-title":"Advancing our understanding of infant bronchiolitis through phenotyping and endotyping: Clinical and molecular approaches","volume":"10","author":"Hasegawa","year":"2016","journal-title":"Expert. Rev. Respir. Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Fauroux, B., Hasco\u00ebt, M., Jarreau, H., Magny, F., Roz\u00e9, C., Saliba, E., and Schwarzinger, M. (2020). Risk factors for bronchiolitis hospitalization in infants: A French nationwide retrospective cohort study over four consecutive seasons (2009\u20132013). PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0229766"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.iac.2019.03.005","article-title":"Infant Immune Response to Respiratory Viral Infections","volume":"39","author":"Heinonen","year":"2019","journal-title":"Immunol. Allergy Clin. North. Am."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"V\u00e1zquez, Y., Gonz\u00e1lez, L., Noguera, L., Gonz\u00e1lez, P.A., Riedel, C.A., Bertrand, P., and Bueno, S.M. (2019). Cytokines in the Respiratory Airway as Biomarkers of Severity and Prognosis for Respiratory Syncytial Virus Infection: An Update. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01154"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s12026-014-8540-1","article-title":"The CD4 T cell response to respiratory syncytial virus infection","volume":"59","author":"Christiaansen","year":"2014","journal-title":"Immunol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1111\/pai.12919","article-title":"Analysis of the immune response in infants hospitalized with viral bronchiolitis shows different Th1\/Th2 profiles associated with respiratory syncytial virus and human rhinovirus","volume":"29","author":"Fedele","year":"2018","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/jmv.25587","article-title":"Clinical and Th1\/Th2 immune response features of hospitalized children with human rhinovirus infection","volume":"92","author":"Yuan","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e326","DOI":"10.1097\/INF.0000000000001299","article-title":"Viral Bronchiolitis is Associated with Altered Cytokine Gene Expression and Lymphocyte Activation Status","volume":"35","author":"Leahy","year":"2016","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jmii.2022.08.013","article-title":"Clinical characteristics and differential cytokine expression in hospitalized Taiwanese children with respiratory syncytial virus and rhinovirus bronchiolitis","volume":"56","author":"Lee","year":"2023","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_24","unstructured":"West, J.B. (2008). Respiratory Physiology: The Essentials, Lippincott Williams and Wilkins. [8th ed.]."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Trifonova, I., Madzharova, I., Christova, I., Angelova, S., Voleva, S., Yordanova, R., Tcherveniakova, T., Krumova, S., and Korsun, N. (2022). Clinical significance and role of coinfections with respiratory pathogens among individuals with confirmed severe acute respiratory syndrome coronavirus-2 infection. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.959319"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1046\/j.1365-2249.2003.02039.x","article-title":"Interferon-gamma levels in nasopharyngeal secretions of infants with respiratory syncytial virus and other respiratory viral infections","volume":"131","author":"Joshi","year":"2003","journal-title":"Clin. Exp. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3345\/kjp.2017.60.9.296","article-title":"Comparison of cytokine expression profiles in infants with a rhinovirus induced lower respiratory tract infection with or without wheezing: A comparison with respiratory syncytial virus","volume":"60","author":"Roh","year":"2017","journal-title":"Korean J. Pediatr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1128\/CMR.00090-16","article-title":"The Human Immune Response to Respiratory Syncytial Virus Infection","volume":"30","author":"Russell","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"883","DOI":"10.2217\/fvl.15.55","article-title":"Genes associated with RSV lower respiratory tract infection and asthma: The application of genetic epidemiological methods to understand causality","volume":"10","author":"Larkin","year":"2015","journal-title":"Future Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.4049\/jimmunol.1100764","article-title":"Multiple CD4+ T cell subsets produce immunomodulatory IL-10 during respiratory syncytial virus infection","volume":"187","author":"Weiss","year":"2011","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Loebbermann, J., Schnoeller, C., Thornton, H., Durant, L., Sweeney, N.P., Schuijs, M., O\u2019Garra, A., Johansson, C., and Openshaw, P.J. (2012). IL-10 regulates viral lung immunopathology during acute respiratory syncytial virus infection in mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032371"},{"key":"ref_32","first-page":"81","article-title":"Soluble interleukin-2 receptor (sCD25) and interleukin-10 plasma concentrations are associated with severity of primary respiratory syncytial virus (RSV) infection","volume":"16","author":"Alonso","year":"2005","journal-title":"Eur. Cytokine Netw."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1086\/380908","article-title":"Influence of promoter variants of interleukin-10, interleukin-9, and tumor necrosis factor-alpha genes on respiratory syncytial virus bronchiolitis","volume":"189","author":"Hoebee","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1093\/infdis\/jis721","article-title":"Innate immune dysfunction is associated with enhanced disease severity in infants with severe respiratory syncytial virus bronchiolitis","volume":"207","author":"Mella","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1164\/ajrccm.161.5.9904078","article-title":"Monocyte IL-10 production during respiratory syncytial virus bronchiolitis is associated with recurrent wheezing in a one-year follow-up study","volume":"161","author":"Bont","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/1465-9921-12-121","article-title":"Local interleukin-10 production during respiratory syncytial virus bronchiolitis is associated with post-bronchiolitis wheeze","volume":"12","author":"Schuurhof","year":"2011","journal-title":"Respir. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/cei.12059","article-title":"Dual role of interleukin-10 in the regulation of respiratory syncitial virus (RSV)-induced lung inflammation","volume":"172","author":"Sun","year":"2013","journal-title":"Clin. Exp. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e02073-24","DOI":"10.1128\/spectrum.02073-24","article-title":"Infection of nonclassic monocytes by respiratory syncytial virus induces an imbalance in the CD4+ T-cell subset response","volume":"13","author":"Han","year":"2025","journal-title":"Microbiol. Spectr."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ding, Q., Xu, L., Zhu, Y., Xu, B., Chen, X., Duan, Y., Xie, Z., and Shen, K. (2020). Comparison of clinical features of acute lower respiratory tract infections in infants with RSV\/HRV infection, and incidences of subsequent wheezing or asthma in childhood. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-020-05094-4"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Hurme, P., Komulainen, M., Tulkki, M., Leino, A., R\u00fcckert, B., Turunen, R., Vuorinen, T., Akdis, M., Akdis, C.A., and Jartti, T. (2022). Cytokine expression in rhinovirus- vs. respiratory syncytial virus-induced first wheezing episode and its relation to clinical course. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1044621"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hurme, P., K\u00e4hk\u00f6nen, M., R\u00fcckert, B., Vahlberg, T., Turunen, R., Vuorinen, T., Akdis, M., Akdis, C.A., and Jartti, T. (2024). Disease Severity and Cytokine Expression in the Rhinovirus-Induced First Wheezing Episode. Viruses, 16.","DOI":"10.3390\/v16060924"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/ppul.21248","article-title":"Toll-like receptor 4 Asp299Gly polymorphism in respiratory syncytial virus epidemics","volume":"45","author":"Marttila","year":"2010","journal-title":"Pediatr. Pulmonol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.gene.2017.12.022","article-title":"Association between single nucleotide polymorphisms in TLR4, TLR2, TLR9, VDR, NOS2 and CCL5 genes with acute viral bronchiolitis","volume":"645","author":"Alvarez","year":"2018","journal-title":"Gene"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1172\/JCI75183","article-title":"TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization","volume":"125","author":"Caballero","year":"2015","journal-title":"J. Clin. Investig."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/5\/426\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:23:01Z","timestamp":1760030581000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/5\/426"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,27]]},"references-count":44,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["pathogens14050426"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14050426","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,27]]}}}