Sputum cytokine mapping reveals an ‘IL‐5, IL‐17A, IL‐25‐high’ pattern associated with poorly controlled asthma

Seys, Sven; Grabowski, Marcin; Adriaensen, Wim; Decraene, Ann; Dilissen, Ellen; Vanoirbeek, Jeroen; Dupont, Lieven; Ceuppens, Jan L.; Bullens, Dominique

doi:10.1111/cea.12125

Cited by 70 publications

(77 citation statements)

References 38 publications

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“…Although there was a significant increase in IL-25 in the group of subjects with asthma, many subjects in the group had normal IL-25 levels. This is consistent with a recent report that IL-25 transcript level was increased in induced sputum from some individuals with asthma (34). None of our subjects were using oral corticosteroids or ICS or leukotriene antagonist before enrollment, which excludes the possibility that prior antiinflammatory medications accounted for differences in IL-25 expression.…”

Section: Discussionsupporting

confidence: 92%

Epithelial Interleukin-25 Is a Key Mediator in Th2-High, Corticosteroid-Responsive Asthma

Cheng

Xue

et al. 2014

Am J Respir Crit Care Med

153

122

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Rationale: Activation of type 2 cytokine pathways plays a central role in a large subset of subjects with asthma. Th2-high and Th2-low asthma have distinct clinical, pathologic, and molecular phenotypes and respond differently to therapy. The factors that initiate type 2 responses in some subjects with asthma are unknown.Objectives: To determine whether expression of epithelial cytokines IL-25, IL-33, and thymic stromal lymphopoietin are associated with type 2 responses and predict response to inhaled corticosteroid (ICS) in asthma.Methods: We analyzed pulmonary function tests, blood, and bronchoscopic biopsies from 21 healthy control subjects and 43 subjects with asthma. Subjects with asthma underwent an 8-week treatment with inhaled budesonide.Measurements and Main Results: Epithelial expression of IL-25, but not IL-33 or thymic stromal lymphopoietin, was increased in a subset of subjects with asthma. The IL-25-high subset had greater airway hyperresponsiveness, more airway and blood eosinophils, higher serum IgE, more subepithelial thickening, and higher expression of Th2 signature genes. ICS improved FEV 1 and hyperresponsiveness in the IL-25-high but not the IL-25-low subset. Plasma IL-25 levels correlated with epithelial IL-25 expression, airway eosinophilia, and beneficial responses to ICS treatment.Conclusions: IL-25 measurements identify two subsets of subjects with distinct asthma phenotypes and different responses to ICS. Because IL-25 has a major role in triggering type 2 responses, bronchial epithelial IL-25 expression is likely a key determinant of type 2 response activation in asthma. Plasma IL-25 level reflects airway IL-25/type 2 response activation and may be useful for predicting responses to asthma therapy.

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Section: Discussionsupporting

confidence: 92%

Epithelial Interleukin-25 Is a Key Mediator in Th2-High, Corticosteroid-Responsive Asthma

Cheng

Xue

et al. 2014

Am J Respir Crit Care Med

153

122

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“…Unfortunately, no information on atopy was provided in this study. However, SEYS et al [75] obtained evidence that high levels of mRNA for IL-25 in sputum cells, just like high mRNA levels for IL-17A, are increased in patients with stable asthma compared with healthy control subjects. However, both groups included atopic subjects so the role of allergy is difficult to evaluate for this study but, of clinical interest, a pattern of particularly high levels of mRNA for IL-25, IL-5 and IL-17A was associated with poorly controlled asthma.…”

Section: Interleukin-25mentioning

confidence: 99%

Interleukin-17 cytokine signalling in patients with asthma

Lindén

Dahlén

2014

Eur Respir J

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Asthma remains a global health problem and, therefore, more effective pharmacotherapy is needed. This is particularly true for chronic and severe asthma. In these clinical phenotypes, chronic inflammation involving neutrophils is likely to play a pathogenic role, making it interesting to target cytokine signalling involved in the accumulation of neutrophils. Therefore, it is of interest that the archetype T-helper 17 cell cytokine interleukin (IL)-17A, perhaps also IL-17F, controls neutrophil accumulation, mucus secretion, macrophage mobilisation and smooth muscle reactivity in various experimental airway models. However, much less is known about the involvement of signalling via IL-17 cytokines in humans with asthma. Existing evidence suggests that these cytokines are released from several types of immune cells in asthma and, for IL-17A, there is a local increase associated with disease severity, with the mobilisation of neutrophils and smooth muscle cells locally in the airways. Even though the causative role of IL-17 cytokines remains unclear, there is potential for clinical utility in targeting IL-17A specifically in patients with moderate-to-severe asthma and high reversibility. There is a need for new and well-powered clinical investigations of signalling via IL-17 cytokines in this clinical phenotype. @ERSpublications There is potential utility for drugs targeting IL-17 cytokine signalling in a sub-group of patients with asthma

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“…In the study no precise answer was given. However, it should be noted that despite the lack of clear results, respondents among whom higher concentration of IL-25 interleukin was identified [17] suffered from severe asthma [6] or moderate asthma [4]; among them were also volunteers [4]. However, they all had positive familial history of allergic diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Cytokines are molecules of a glycoprotein, and they regulate many vital functions of cells. They are involved in inflammatory reactions and in the regulation of immune and haematopoietic processes [4][5][6][7]. Frequently they have a pleiotropic mechanism of action (the ability to act on various cells and induce various effects) and redundancy (when different cytokines produce the same effect).…”

Section: Introductionmentioning

confidence: 99%

Assessment of concentrations of interleukin-25 in bronchial asthma – preliminary studies

Czarny-Działak¹,

Słuszniak²

2016

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Introduction: Studies have demonstrated an important role of cytokines in the development of asthma, in particular the balance between them disturbed in favour of pro-inflammatory cytokines. belongs to the family of cytokines from IL-17. Its role in the pathogenesis of allergic diseases of the respiratory tract is not entirely clear. The study took into account the fact that the role can be very important due to the dual mechanism of action as an anti-inflammatory and inflammatory stimulant. Aim of the research: To assess whether the concentration of IL-25 depends on the the severity of the course of asthma. Material and methods: The study involved 80 people: 20 volunteers and 60 patients with asthma -20 people with mild persistent asthma, 20 with moderate, and with 20 severe. All patients were maintained on a course of asthma control. From each patient, blood was drawn to assess IL-25 ELISA test; all patients also had spirometry performed (in the framework of visits to the clinic). Results: In none of the cases of the people from the examined group there was an increased level of IL-25. However, some subjects (17) had higher levels of this interleukin than other people -among these were four volunteers and 13 patients with asthma. Conclusions: In the future patients should be checked during exacerbations of asthma and have the response time tried to be extended to maximum so that we can measure lower concentrations, which within a standard procedure could has not been varied (found below the lowest standard).

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Sputum cytokine mapping reveals an ‘IL‐5, IL‐17A, IL‐25‐high’ pattern associated with poorly controlled asthma

Cited by 70 publications

References 38 publications

Epithelial Interleukin-25 Is a Key Mediator in Th2-High, Corticosteroid-Responsive Asthma

Epithelial Interleukin-25 Is a Key Mediator in Th2-High, Corticosteroid-Responsive Asthma

Interleukin-17 cytokine signalling in patients with asthma

Assessment of concentrations of interleukin-25 in bronchial asthma – preliminary studies

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