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 pro-inflammatory cytokines. We aimed to investigate the possible role of IL-26 in severe asthma. We analyzed the expression of IL-26 in severe asthma both in peripheral blood and induced sputum. A total of 50 adult women with severe asthma were recruited and compared to 30 healthy controls (HC). ELISA defined serum and sputum fluid (SF) levels of IL-26 and IL-17. IL-26 mRNA expression and IL-26 protein were analyzed 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.

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.

These findings show that IL-26 is highly produced in asthmatic sputum, induces pro-inflammatory cytokine secretion by monocytes/macrophages, and favors 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.