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Ritter, M.* ; Straubinger, K.* ; Schmidt, S.* ; Busch, D.H. ; Hagner, S.* ; Garn, H.* ; da Costa, C.P.* ; Layland, L.E.*

Functional relevance of NLRP3 inflammasome-mediated interleukin (IL)-1 beta during acute allergic airway inflammation.

Clin. Exp. Immunol. 178, 212-223 (2014)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Overall asthmatic symptoms can be controlled with diverse therapeutic agents. However, certain symptomatic individuals remain at risk for serious morbidity and mortality, which prompts the identification of novel therapeutic targets and treatment strategies. Thus, using an adjuvant-free T helper type 2 (Th2) murine model, we have deciphered the role of interleukin (IL)-1 signalling during allergic airway inflammation (AAI). Because functional IL-1 beta depends on inflammasome activation we first studied asthmatic manifestations in specific inflammasome-deficient [NACHT, LRR and PYD domains-containing protein 3 (NLRP3(-/-)) and apoptosis-associated specklike protein containing a caspase recruitment domain (ASC(-/-))] and IL-1 receptor type 1(-/-) (IL-1R1(-/-)) mice on the BALB/c background. To verify the onset of disease we assessed cellular infiltration in the bronchial regions, lung pathology, airway hyperresponsiveness and ovalbumin (OVA)-specific immune responses. In the absence of NLRP3 inflammasome-mediated IL-1 beta release all symptoms of AAI were reduced, except OVA-specific immunoglobulin levels. To address whether manipulating IL-1 signalling reduced asthmatic development, we administered the IL-1R antagonist anakinra (Kineret (R)) during critical immunological time-points: sensitization or challenge. Amelioration of asthmatic symptoms was only observed when anakinra was administered during OVA challenge. Our findings indicate that blocking IL-1 signalling could be a potential complementary therapy for allergic airway inflammation.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Allergy ; Anakinra ; Il-1 Receptor Antagonist ; Il-1 Beta ; Nlrp3-inflammasome; Adaptive Immune-responses; Nalp3 Inflammasome; Receptor Antagonist; Lung Inflammation; Extracellular Atp; Family-members; Induced Asthma; T-cells; Mice; Model
ISSN (print) / ISBN 0009-9104
e-ISSN 1365-2249
Journal Clinical & Experimental Immunology
Quellenangaben Volume: 178, Issue: 2, Pages: 212-223 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)