Cytokine responses to two common respiratory pathogens in children are dependent on interleukin-1β

dc.contributor.authorChen AC, Xi Y, Carroll M, Petsky HL, Gardiner SJ, Pizzutto SJ, Yerkovich ST, Baines KJ, Gibson PG, Hodge S, Masters IB, Buntain HM, Chang AB, Upham JW.,
dc.date.issued2017
dc.description.abstractProtracted bacterial bronchitis (PBB) in young children is a common cause of prolonged wet cough and may be a precursor to bronchiectasis in some children. Although PBB and bronchiectasis are both characterised by neutrophilic airway inflammation and a prominent interleukin (IL)-1β signature, the contribution of the IL-1β pathway to host defence is not clear. This study aimed to compare systemic immune responses against common pathogens in children with PBB, bronchiectasis and control children and to determine the importance of the IL-1β pathway. Non-typeable Haemophilus influenzae (NTHi) stimulation of peripheral blood mononuclear cells (PBMCs) from control subjects (n=20), those with recurrent PBB (n=20) and bronchiectasis (n=20) induced high concentrations of IL-1β, IL-6, interferon (IFN)-γ and IL-10. Blocking with an IL-1 receptor antagonist (IL-1Ra) modified the cellular response to pathogens, inhibiting cytokine synthesis by NTHi-stimulated PBMCs and rhinovirus-stimulated PBMCs (in a separate PBB cohort). Inhibition of IFN-γ production by IL-1Ra was observed across multiple cell types, including CD3+ T cells and CD56+ NK cells. Our findings highlight the extent to which IL-1β regulates the cellular immune response against two common respiratory pathogens. While blocking the IL-1β pathway has the potential to reduce inflammation, this may come at the cost of protective immunity against NTHi and rhinovirus.
dc.description.statementofresponsibilityAlice C-H. Chen, Yang Xi, Melanie Carroll, Helen L. Petsky, Samantha J. Gardiner, Susan J. Pizzutto, Stephanie T. Yerkovich, Katherine J. Baines, Peter G. Gibson, Sandra Hodge, Ian B. Masters, Helen M. Buntain, Anne B. Chang and John W. Upham
dc.identifier.citationERJ Open Research, 2017; 3(4):1-10
dc.identifier.doi10.1183/23120541.00025-2017
dc.identifier.issn2312-0541
dc.identifier.issn2312-0541
dc.identifier.urihttp://hdl.handle.net/2440/116027
dc.language.isoen
dc.publisherPubMed Central
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1058213
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1058552
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1042601
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1040830
dc.rights© ERS 2017. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.
dc.source.urihttps://doi.org/10.1183/23120541.00025-2017
dc.titleCytokine responses to two common respiratory pathogens in children are dependent on interleukin-1β
dc.title.alternativeCytokine responses to two common respiratory pathogens in children are dependent on interleukin-1beta
dc.typeJournal article
pubs.publication-statusPublished

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