Enhanced local production of IL-26 in uncontrolled compared with controlled adult asthma

Tufvesson, Ellen; Jogdand, Prajakta; Fru, Karlhans; Levänen, Bettina; Erjefält, Jonas; Bjermer, Leif; Lindén, Anders

doi:10.1016/j.jaci.2019.06.035

Cited by 9 publications

(14 citation statements)

References 15 publications

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“…35 However, our results contrast with data on IL-26 in BAL in adult patients that were lower than those observed in healthy controls, despite a positive correlation between IL-26 and FeNO. 35 This may be linked to the degree of asthma severity as in the study of Tufvesson et al, asthma was reported as mild or moderate. 35 The lowest level observed in controlled asthma compared to uncontrolled and severe asthma was associated with a clinical response to corticosteroid.…”

Section: Discussioncontrasting

confidence: 99%

“…In a similar way, uncontrolled asthma, in children and adults was characterized by an increase in IL-26 levels compared to controlled cases. 8,35 Further, we observed a negative correlation between IL-26 levels and FEV1, confirming previous studies. 35 However, our results contrast with data on IL-26 in BAL in adult patients that were lower than those observed in healthy controls, despite a positive correlation between IL-26 and FeNO.…”

Section: Discussionsupporting

confidence: 91%

“…8,35 Further, we observed a negative correlation between IL-26 levels and FEV1, confirming previous studies. 35 However, our results contrast with data on IL-26 in BAL in adult patients that were lower than those observed in healthy controls, despite a positive correlation between IL-26 and FeNO. 35 This may be linked to the degree of asthma severity as in the study of Tufvesson et al, asthma was reported as mild or moderate.…”

Section: Discussionsupporting

confidence: 91%

“…35 This may be linked to the degree of asthma severity as in the study of Tufvesson et al, asthma was reported as mild or moderate. 35 The lowest level observed in controlled asthma compared to uncontrolled and severe asthma was associated with a clinical response to corticosteroid. In vitro, hydrocortisone, a corticosteroid, inhibited IL-26 production from lung fibroblasts.…”

Section: Discussionmentioning

confidence: 98%

“…14,18 A local production has been demonstrated by bronchial and lung biopsies with immunostaining of bronchial epithelial cells and macrophages/ monocytes. 35 Lung fibroblasts participate as well to IL26 production. 36 Our data show an increased concentration of IL-26 in sputum fluid from severe asthma patients compared IL-26 present in the sputum fluid of asthmatic patients is biologically active.…”

Section: Discussionmentioning

confidence: 99%

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<p>Sputum IL-26 Is Overexpressed in Severe Asthma and Induces Proinflammatory Cytokine Production and Th17 Cell Generation: A Case–Control Study of Women</p>

Louhaichi¹,

Mlika²,

Hamdi³

et al. 2020

JAA

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Objective: Asthma inflammation is a complex pathway involving numerous mediators. Interleukin-26 (IL-26), a member of the IL-10 cytokine family, is abundant in human airways and induces the production of proinflammatory cytokines. Our aim was to investigate the possible role of IL-26 in severe asthma. We analysed the expression of IL-26 in severe asthma both in peripheral blood and induced sputum. Patients and Methods: A total of 50 adult women with severe asthma were recruited and compared to 30 healthy controls (HC). Serum and sputum fluid (SF) levels of IL-26 and IL-17 were defined by ELISA. IL-26 mRNA expression and IL-26 protein were analysed using RT-PCR and Western blot. In vitro, we studied the effect of recombinant IL-26 (rIL-26) and SF-IL-26 on cultured CD4 + T cells and monocytes, comparing patients and controls. Results: Concentrations of IL-26 are higher in serum and induced sputum of asthmatic patients than in HC. Moreover, IL-26 protein and mRNA expression were significantly elevated in asthma sputum cells compared to PBMCs. We observed a positive correlation between body mass index (BMI) and sputum fluid IL-26, while the correlation between IL-26 and lung function tests (FEV1% and FEV1/FVC ratio) was negative. IL-17A was highly expressed in SF and correlated positively with IL-26. In patients' sputum IL-26 and IL-17A were significantly associated with neutrophils. Stimulation of cultured CD4 + T cells with monocytes by recombinant IL-26 promoted the generation of RORγt + Th17 + cells inducing the production of IL-17A, IL-1β, IL-6 and TNF-α cytokines. IL-26 expressed in SF was biologically active and induced IL-17 secretion in the presence of IL-1β and IL-6 cytokines. Conclusion: These findings show that IL-26 is highly produced in asthmatic sputum, induces pro-inflammatory cytokine secretion by monocytes/macrophages, and favours Th17 cell generation. IL-26 thereby appears as a novel pro-inflammatory cytokine, produced locally in the airways that may constitute a promising target to treat asthma inflammatory process.

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Section: Discussioncontrasting

confidence: 99%