Evidence map›Paper›PMID 41099307›Full record

ArticleAllergy2026

Immune Training of the Interleukin 6 Gene in Airway Epithelial Cells is Central to Asthma Exacerbations.

Lars P Lunding, Markus Weckmann, Ulrich M Zissler, Constanze Jakwerth, Rebecca Bodenstein-Sgró, Sina Webering, Christina Vock, Johanna C Ehlers, Romina A M Fernandez Ceballos, Sai Sneha Priya Nemani and 25 more

Abstract read
In one paragraph

Article in Allergy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

35 authors.

Lars P LundingDivision of Lung Immunology, Priority Area Chronic Lung Diseases, Research Centre Borstel - Leibniz Lung Centre, Borstel, Germany.ORCID https://orcid.org/0000-0002-5278-3129
Markus WeckmannAirway Research Centre North, Member of the German Centre for Lung Research (DZL), Germany.
Ulrich M ZisslerCentre of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Centre Munich, Munich, Germany.
Constanze JakwerthCentre of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Centre Munich, Munich, Germany.ORCID https://orcid.org/0000-0002-2902-0393
Rebecca Bodenstein-SgróDivision of Lung Immunology, Priority Area Chronic Lung Diseases, Research Centre Borstel - Leibniz Lung Centre, Borstel, Germany.
Sina WeberingDivision of Lung Immunology, Priority Area Chronic Lung Diseases, Research Centre Borstel - Leibniz Lung Centre, Borstel, Germany.
Christina VockAirway Research Centre North, Member of the German Centre for Lung Research (DZL), Germany.
Johanna C EhlersAirway Research Centre North, Member of the German Centre for Lung Research (DZL), Germany.
Romina A M Fernandez CeballosAirway Research Centre North, Member of the German Centre for Lung Research (DZL), Germany.
Sai Sneha Priya NemaniAirway Research Centre North, Member of the German Centre for Lung Research (DZL), Germany.ORCID https://orcid.org/0009-0004-3625-3373
Karosham Diren ReddyAirway Research Centre North, Member of the German Centre for Lung Research (DZL), Germany.
Brian George G OliverSchool of Medical and Molecular Biosciences, University of Technology Sydney, Australia.
Cornelis J VermeulenUniversity Medical Centre Groningen, Department of Pulmonary Diseases, GRIAC, the Netherlands.ORCID https://orcid.org/0000-0002-3280-1414
Maarten van de BergeUniversity Medical Centre Groningen, Department of Pulmonary Diseases, GRIAC, the Netherlands.
Carole OberDepartment of Human Genetics, University of Chicago, Chicago, Illinois, USA.
Axel KünstnerLuebeck Institute of Experimental Dermatology and Institute for Cardiogenetics, University of Luebeck, Luebeck, Germany.
Hauke BuschLuebeck Institute of Experimental Dermatology, Institute for Cardiogenetics and Centre for Research of Inflammatory Skin Disease (CRIS), University of Luebeck, Luebeck, Germany.
Inke KönigAirway Research Centre North, Member of the German Centre for Lung Research (DZL), Germany.
Christoph GarbersInstititute for Clinical Biochemistry, Hannover Medical School, Hannover, Germany.ORCID https://orcid.org/0000-0003-4939-6950
Carsten B Schmidt-WeberCentre of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Centre Munich, Munich, Germany.ORCID https://orcid.org/0000-0002-3203-8084
Marcel F NoldDepartment of Paediatrics, Monash University, Melbourne, Victoria, Australia.
Ali Önder YildirimComprehensive Pneumology Centre Munich (CPC-M), Member of the German Centre for Lung Research (DZL), Germany.
Claudia A Nold-PetryDepartment of Paediatrics, Monash University, Melbourne, Victoria, Australia.
Zane OrinskaAirway Research Centre North, Member of the German Centre for Lung Research (DZL), Germany.
Thomas BahmerAirway Research Centre North, Member of the German Centre for Lung Research (DZL), Germany.
Jan HeyckendorfAirway Research Centre North, Member of the German Centre for Lung Research (DZL), Germany.
Gesine HansenTranslational Paediatric Pneumology, Department of Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
Erika von MutiusTechnology Transfer Center for Building Biology and Indoor Health, Rosenheim Technical University of Applied Sciences, Freilassing, Germany.
Klaus F RabeAirway Research Centre North, Member of the German Centre for Lung Research (DZL), Germany.ORCID https://orcid.org/0000-0002-7020-1401
Anna-Maria DittrichTranslational Paediatric Pneumology, Department of Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
Bianca SchaubComprehensive Pneumology Centre Munich (CPC-M), Member of the German Centre for Lung Research (DZL), Germany.ORCID https://orcid.org/0000-0003-1652-8873
Folke BrinkmannAirway Research Centre North, Member of the German Centre for Lung Research (DZL), Germany.
Matthias V KoppAirway Research Centre North, Member of the German Centre for Lung Research (DZL), Germany.
Michael WegmannDivision of Lung Immunology, Priority Area Chronic Lung Diseases, Research Centre Borstel - Leibniz Lung Centre, Borstel, Germany.ORCID https://orcid.org/0000-0002-1658-1554
ALLIANCE Study Group as part of the German Centre for Lung Research (DZL)

Funding

cGMP Manufacture, Fill-Finish, Release, Analytical and Stability Testing and Stability Program of a Nanoparticle Based HIV Envelope Vaccine75N93022D00005 · NIAID · INTERNATIONAL AIDS VACCINE INITIATIVE · PI HASSELL, THOMAS · 2022 to 2025
$8.0M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00005 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WATSON, KAROL E · 2020 to 2025
$5.1M
Bavarian State Office for Health and Food Safety LGL;K1-2497-GLB-20-V4Deutsches Zentrum für LungenforschungNHLBI NIH HHS 75N92020D00005NIAID NIH HHS 75N93022D00005NIAID NIH HHS 75N93023D00005NIDA NIH HHS 75N95020D00005ORFDO NIH HHS 75N99020D00005
6 · The paper itself

Abstract

questionEpidemiological studies suggest that respiratory viral infections are major triggers of asthma exacerbations, and clinical studies have suggested the involvement of an increased interleukin-6 (IL-6) release. What is the pathophysiological role of IL-6 in asthma exacerbation, and which mechanisms lead to enhanced IL-6 release? MATERIALS AND

methodsExacerbations of ovalbumin-induced experimental allergic asthma were elicited in wild-type and IL-6-deficient mice by intranasal (i.n.) application of poly(I:C). Airway inflammation, cytokine expression and release, mucus production and airway hyperresponsiveness were measured. IL-6 was neutralised by i.n. anti-IL-6 antibody application. The human bronchial epithelial cell line, BEAS-2B, was stimulated with poly(I:C) and infected with human rhinovirus-16 in vitro, followed by quantification of IL6 gene expression and DNA methylation. Genome-wide DNA methylation was assessed in bronchial epithelial cells from adults with asthma (cohort I, n = 54) and in nasal epithelial cells from children and adults in the All-Age-Asthma cohort (ALLIANCE, n = 53 and n = 108 respectively).

resultsPoly(I:C)-induced experimental exacerbations in mice were preceded and paralleled by exaggerated IL-6 release in the airway epithelium, with IL-6 neutralisation completely preventing experimental exacerbations. Repetitive infection/stimulation with RV16 or poly(I:C) resulted in training of the IL-6 release in human respiratory epithelial cells. In patients, hypomethylation at the IL6 gene methylation was associated with high IL6 expression and future exacerbations. ANSWER: An exaggerated IL-6 release is required for exacerbation of experimental asthma, potentially the result of viral PAMP-induced immune training of airway epithelial cells. Additionally, patients with asthma carrying the epigenetic signature of a trained IL-6 response exacerbate more frequently. These findings open new avenues to identify and treat exacerbation-prone patients.

Indexed as

AsthmaEpithelial CellsInterleukin-6Respiratory MucosaAdultAnimalsCell LineDisease Models, AnimalDisease ProgressionDNA MethylationFemaleHumansMaleMiceInterleukin-6asthmaexacerbationsIL‐6immune trainingrespiratory viruses

Identifiers

PMID41099307
PMCPMC12773691

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.