Abstract
BackgroundAsthma is a disease encompassing a variety of contributing factors. Phenotyping of asthma based on the profile of accumulated granulocytes in the airways has been performed to explore the mediators involved in allergic bronchial inflammation. The aim of this study was to clarify the characteristics of the CXC chemokine superfamily induced by IFN-γ, namely CXCR3 ligands, in the airways of patients with asthma stratified by the differential proportion of granulocytes in sputum.MethodsSputum was induced in 39 adult patients with asthma and 12 healthy subjects. Sputum samples were analyzed for total cell counts and differentials, and concentrations of IFN-γ–inducible protein 10 kDa (IP-10, CXCL10), monokine induced by IFN-γ (Mig, CXCL9), IFN-inducible T cell a chemoattractant (I-TAC, CXCL11), and IL-8 in the supernatants were assayed by ELISA.ResultsSputum concentrations of IP-10, Mig, and IL-8 were significantly higher in asthma than in healthy subjects. IP-10, Mig, and IL-8 were significantly higher in the mixed granulocyte subtype (eosinophils ≥ 2 % and neutrophils ≥ 40 % in sputum) than in healthy subjects. Additionally, IP-1 0 was significantly higher in the mixed granulocyte subtype than in eosinophil-predominant or neutrophil-predominant subtype (eosinophil percentage ≥ 2 % or neutrophil percentage ≥ 40 %). Mig and IL-8 were significantly higher in the mixed granulocyte subtype than in the paucigranulocyte subtype (eosinophils < 2 % and neutrophils < 40 % in sputum). I-TAC was not different between healthy subjects and asthmatics or granulocyte subtypes. All CXCR3 ligands were significantly associated with the composite of the eosinophil and neutrophil ratio in patients with asthma. Only Mig was significantly correlated with the total eosinophil and neutrophil ratio in patients with asthma on adjusted partial correlation analysis. Mig and IL-8 were significantly negatively correlated with forced expiratory volume in 1 s % predicted (% FEV1) in patients with asthma.ConclusionsCXCR3 ligands may serve as potent promoters in eosinophilic and neutrophilic airway inflammation in asthma.Electronic supplementary materialThe online version of this article (doi:10.1186/s40733-016-0021-y) contains supplementary material, which is available to authorized users.
Highlights
Asthma is a disease encompassing a variety of contributing factors
This study showed that sputum FN-γ–inducible protein 10 kDa (IP-10) and monokine induced by IFN-γ (Mig), members of the CXCR3 ligands family, and IL-8 were higher in asthma patients than in healthy subjects
According to the classification based on the proportion of inflammatory granulocytes in sputum, IP-10, Mig and IL8 in sputum were higher in the mixed granulocyte subtype
Summary
Asthma is a disease encompassing a variety of contributing factors. Phenotyping of asthma based on the profile of accumulated granulocytes in the airways has been performed to explore the mediators involved in allergic bronchial inflammation. Asthma endotype cluster analysis followed by genotype or phenotype cluster analysis has achieved successful clinical results, including anti-IL-5 antibody therapy for persistent eosinophilic severe asthma and anti- IL-4 or anti-IL-13 antibody therapy for high-Th2-type severe asthma [9,10,11,12]. These results imply that endotype cluster analysis is an important approach for determining the treatment of asthma. Two Severe Asthma Research Program (SARP) studies reported that moderate-to-severe asthma was characterized by neutrophil-predominant or mixed granulocytic inflammation [21, 22]. The stratification of asthma based on the predominant granulocyte in sputum has shown elevation of some cytokines or chemokines [21,22,23,24,25,26,27,28]
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