University of Oulu

Hurme P, Komulainen M, Tulkki M, Leino A, Rückert B, Turunen R, Vuorinen T, Akdis M, Akdis CA and Jartti T (2022) Cytokine expression in rhinovirus- vs. respiratory syncytial virus-induced first wheezing episode and its relation to clinical course. Front. Immunol. 13:1044621. doi: 10.3389/fimmu.2022.1044621

Cytokine expression in rhinovirus- vs. respiratory syncytial virus-induced first wheezing episode and its relation to clinical course

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Author: Hurme, Pekka1; Komulainen, Miisa1; Tulkki, Marleena1;
Organizations: 1Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland
2Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland
3New Children’s Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
4Institute of Biomedicine, University of Turku, Turku, Finland
5Department of Clinical Microbiology, Turku University Hospital, Turku, Finland
6PEDEGO Research Unit, Medical Research Center, University of Oulu, Oulu, Finland
7Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.4 MB)
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Language: English
Published: Frontiers Media, 2022
Publish Date: 2023-07-05


Rhinovirus (RV) and respiratory syncytial virus (RSV) are common causes of bronchiolitis. Unlike an RSV etiology, an RV etiology is associated with a markedly increased risk of asthma. We investigated the cytokine profiles of RV- and RSV-induced first wheezing episode and their correlation with prognosis. We recruited 52 sole RV- and 11 sole RSV-affected children with a severe first wheezing episode. Peripheral blood mononuclear cells (PBMCs) were isolated during acute illness and 2 weeks later and stimulated in vitro with anti-CD3/anti-CD28. Culture medium samples were analyzed for 56 different cytokines by multiplex ELISA. Recurrences were prospectively followed for 4 years. In adjusted analyses, the cytokine response from PBMCs in the RV group was characterized by decreased expression of interleukin 1 receptor antagonist (IL-1RA), interleukin 1 beta (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) and increased expression of eosinophil chemotactic protein 2 (eotaxin-2), thymus- and activation-regulated chemokine (TARC), and epithelial-derived neutrophil-activating peptide 78 (ENA-78) in the acute phase and increased expression of fractalkine in the convalescent phase compared to those in the RSV group. An analysis of the change in cytokine expression between study points revealed an increased expression of fractalkine and IL-1β and decreased expression of I-309 (CCL1) and TARC in the RV group compared to those in the RSV group.. Considering hospitalization time, a significant non-adjusted group × cytokine interaction was observed in the levels of interferon gamma (IFN-γ), macrophage-derived chemokine (MDC), IL-1RA, and vascular endothelial growth factor (VEGF), indicating that a higher expression of cytokine was associated with shorter hospitalization time in the RSV group but not in the RV group. A significant interaction was also found in interleukin 6 (IL-6), but the cytokine response was not associated with hospitalization time in the RSV or RV group. In the RV group, increased expression of I-309 (CCL1) and TARC was associated with fewer relapses within 2 months, and decreased expression of interleukin 13 (IL-13) and increased expression of I-309 (CCL1) were associated with less relapses within 12 months. Differences in cytokine response from PBMCs were observed between RV- and RSV-induced first severe wheezing episode. Our findings also reveal new biomarkers for short- and medium-term prognosis in first-time wheezing children infected with RV or RSV.

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Series: Frontiers in immunology
ISSN: 1664-3224
ISSN-E: 1664-3224
ISSN-L: 1664-3224
Volume: 13
Article number: 1044621
DOI: 10.3389/fimmu.2022.1044621
Type of Publication: A1 Journal article – refereed
Field of Science: 3125 Otorhinolaryngology, ophthalmology
Funding: Supported by the Academy of Finland (grant numbers 132595 and 114034), Helsinki; Finnish Medical Foundation, Helsinki; the Sigrid Jusélius Foundation, Helsinki; the Foundation for Pediatric Research, Helsinki; the Finnish Cultural Foundation, Turku and Helsinki; Turku University Foundation, Turku; the Paulo Foundation, Helsinki; and the Allergy Research Foundation, Helsinki – all in Finland. The study was supervised by TJ Leiras Takeda (Helsinki, Finland) who provided prednisolone and placebo preparations, but did not offer any financial support nor required any confidentiality agreements. The granting agencies covered all costs and played no role in the study design, data analysis, or manuscript preparation.
Copyright information: © 2022 Hurme, Komulainen, Tulkki, Leino, Rückert, Turunen, Vuorinen, Akdis, Akdis and Jartti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.