Is IL-1β inhibition the next therapeutic target in asthma?

Peebles, R. Stokes

doi:10.1016/j.jaci.2017.03.018

Cited by 8 publications

(5 citation statements)

References 13 publications

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“…IL-1β has implicated in a number of pulmonary diseases (44–46). Although increases in IL-1β observed herein are not specific to only patients with asthma, IL-1β is emerging as a key cytokine relevant to the pathogenesis of asthma (47). IL-1β has been linked to severe, neutrophilic, steroid insensitive asthma in a mouse model (48).…”

Section: Discussionmentioning

confidence: 88%

IL-1/inhibitory κB kinase ε–induced glycolysis augment epithelial effector function and promote allergic airways disease

Qian

Aboushousha

Wetering

et al. 2018

Journal of Allergy and Clinical Immunology

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Section: Discussionmentioning

confidence: 88%

IL-1/inhibitory κB kinase ε–induced glycolysis augment epithelial effector function and promote allergic airways disease

Qian

Aboushousha

Wetering

et al. 2018

Journal of Allergy and Clinical Immunology

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“…long chain fatty acids, which were not measured specifically in our study, induced IL-1β expression in the lungs. IL-1β could increase bronchial reactivity via up-regulation of T H 2/T H 17 cells, which were associated with severe asthma phenotype in humans 19,20 .…”

Section: Discussionmentioning

confidence: 99%

Caloric restriction prevents the development of airway hyperresponsiveness in mice on a high fat diet

Younas

Vieira

et al. 2019

Sci Rep

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We have previously shown that high fat diet (HFD) for 2 weeks increases airway hyperresponsiveness (AHR) to methacholine challenge in C57BL/6J mice in association with an increase in IL-1β levels in lung tissue. We hypothesize that obesity increases AHR via the IL-1β mechanism, which can be prevented by caloric restriction and IL-1β blockade. In this study, we fed C57BL/6J mice for 8 weeks with several hypercaloric diets, including HFD, HFD supplemented with fructose, high trans-fat diet (HTFD) supplemented with fructose, either ad libitum or restricting their food intake to match body weight to the mice on a chow diet (CD). We also assessed the effect of the IL-1β receptor blocker anakinra. All mice showed the same total respiratory resistance at baseline. All obese mice showed higher AHR at 30 mg/ml of methacholine compared to CD and food restricted groups, regardless of the diet. Obese mice showed significant increases in lung IL-1 β mRNA expression, but not the protein, compared to CD and food restricted mice. Anakinra abolished an increase in AHR. We conclude that obesity leads to the airway hyperresponsiveness preventable by caloric restriction and IL-1β blockade.

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“…There is interest in a role of IL-1β as inducer of IL-17 and IL-6 in asthma. However, since antagonising biologicals have failed to produce acceptable clinical effects, phenotypes or endotypes of asthma where these cytokines have significant roles have yet to be identified [ 32 ]. Based on the present data we suggest that IL-1β is a participating factor in viral induced asthma exacerbations but not in baseline allergic conditions.…”

Section: Discussionmentioning

confidence: 99%

IL-1β mediates lung neutrophilia and IL-33 expression in a mouse model of viral-induced asthma exacerbation

et al. 2018

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BackgroundViral-induced asthma exacerbations, which exhibit both Th1-type neutrophilia and Th2-type inflammation, associate with secretion of Interleukin (IL)-1β. IL-1β induces neutrophilic inflammation. It may also increase Th2-type cytokine expression. We hypothesised that IL-1β is causally involved in both Th1 and Th2 features of asthma exacerbations. This hypothesis is tested in our mouse model of viral stimulus-induced asthma exacerbation.MethodWild-type (WT) and IL-1β deficient (IL-1β−/−) mice received house dust mite (HDM) or saline intranasally during three weeks followed by intranasal dsRNA (PolyI:C molecule known for its rhinovirus infection mimic) for three consecutive days to provoke exacerbation. Bronchoalveolar lavage fluid was analysed for inflammatory cells and total protein. Lung tissues were stained for neutrophilic inflammation and IL-33. Tissue homogenates were analysed for mRNA expression of Muc5ac, CXCL1/KC, TNF-α, CCL5, IL-25, TSLP, IL-33, IL-1β, CCL11 and CCL2 using RT-qPCR.ResultsExpression of IL-1β, neutrophil chemoattractants, CXCL1 and CCL5, the Th2-upstream cytokine IL-33, and Muc5ac were induced at exacerbation in WT mice and were significantly inhibited in IL-1β−/− mice at exacerbation. Effects of HDM alone were not reduced in IL-1β-deficient mice.ConclusionWithout being involved in the baseline HDM-induced allergic asthma, IL-1β signalling was required to induce neutrophil chemotactic factors, IL-33, and Muc5ac expression at viral stimulus-induced exacerbation. We suggest that IL-1β has a role both in neutrophilic and Th2 inflammation at viral-induced asthma exacerbations.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0725-z) contains supplementary material, which is available to authorized users.

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Is IL-1β inhibition the next therapeutic target in asthma?

Cited by 8 publications

References 13 publications

IL-1/inhibitory κB kinase ε–induced glycolysis augment epithelial effector function and promote allergic airways disease

IL-1/inhibitory κB kinase ε–induced glycolysis augment epithelial effector function and promote allergic airways disease

Caloric restriction prevents the development of airway hyperresponsiveness in mice on a high fat diet

IL-1β mediates lung neutrophilia and IL-33 expression in a mouse model of viral-induced asthma exacerbation

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