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

Abstract

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.

Apolipoprotein E is a concentration-dependent pulmonary danger signal that activates the NLRP3 inflammasome and IL-1β secretion by bronchoalveolar fluid macrophages from asthmatic subjects

“…This might be relevant for allergic asthmatic patients with HDM-induced disease who have asthma exacerbations caused by doublestranded RNA viruses, such as influenza, rhinovirus, or respiratory syncytial virus, because IL-1b has been shown to mediate neutrophilic airway inflammation in this setting. 37,38 In addition, our contrasting results from murine models induced by HDM in Apoe-null mice on a C57BL/6 background 8 versus HDM plus poly(I:C) in wild-type mice on a BALB/c background suggest that APOE has contextdependent effects in the setting of neutrophilic compared with eosinophilic airway inflammation, as well as when APOE levels are increased compared with when APOE is absent from the lung.…”

“…Because IL-1b contributes to the pathogenesis of neutrophilic airway inflammation in asthmatic patients, we used a murine model of neutrophilic airway inflammation induced by HDM with subsequent administration of the doublestranded RNA surrogate poly(I:C) to mimic a concurrent virusinduced asthma exacerbation (Fig 4, A). 37,38 Of note, poly(I:C) alone does not induce IL-1b secretion in the mouse lung. 37,39,40 As shown in Fig 4, B, HDM plus poly(I:C) induced a neutrophil-predominant inflammatory phenotype that was associated with significant increases in BALF IL-1b levels (Fig 4, C).…”

The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model

“…Virusderived dsRNA induces inflammatory cytokine production in the respiratory tract of asthma patients and eosinophils and neutrophils accumulate in the respiratory tract, causing asthma exacerbation [40]. Several studies have used antigen (HDM or OVA) and poly(I:C) in virus-induced asthma exacerbation models in mice [41][42][43][44]. The present study therefore examined HDM and poly(I:C) administrations to mimic virus-induced asthma exacerbation.…”

Loss of IL-33 enhances elastase-induced and cigarette smoke extract-induced emphysema in mice

“…IL-33 is a member of the IL-1 family, which acts as a ligand for ST2 (IL-1Ra) [7] and induces not only type 2 cytokines, but also proin ammatory cytokines, such as IL-1β, IL-6, and TNF-α, from mast cells [24] [25] [26] [27] and basophils [8], as well as the type-1 cytokine IFN-γ from NK cells and NKT cells [28] [29]. These proin ammatory cytokines, together with Th1-related immunity, play important roles in the pathogenesis of COPD [30].…”