Influence of serum IL-36 subfamily cytokines on clinical manifestations of asthma.

BACKGROUND: The IL-36 subfamily, a member of the IL-1 superfamily, is thought to promote type 2 (T2) and non-T2 inflammation and involved in autoimmune and airway disease progression. However, its role in asthma remains unclear. OBJECTIVE: We sought to determine the contribution of the IL-36 subfamily to the clinical manifestation of asthma. METHODS: The levels of serum IL-36α, IL-36β, and IL-36γ, recognized as IL-36 subfamily agonists, and IL-36 receptor antagonist (IL-36Ra) and IL-38, recognized as IL-36 subfamily antagonists, were measured by ELISA in 110 asthma patients (55 with nonsevere and 55 with severe asthma) aged ≥20 years and 31 healthy individuals. The association of IL-36 with clinical indices and inflammatory mediators was examined. The characteristics of high and low IL-36 subgroups were explored. RESULTS: IL-36α, IL-36γ, and IL-36Ra levels were significantly higher in asthma patients, especially patients with severe asthma, than in healthy controls. The high IL-36γ group exhibited lower Asthma Control Test scores (P = .01), more frequent asthma exacerbations (AEs), and higher hazard ratio for AEs. The high IL-36Ra group exhibited higher values of forced expiratory volume in 1 second, more frequent severe AEs, and higher hazard ratio for severe exacerbations. The IL-36 cytokine levels, except for IL 36α, were positively correlated with IL-6, IL-13, IL-17, and/or IFN-γ levels. IL-36Ra was positively correlated with age-adjusted forced expiratory volume and forced vital capacity. CONCLUSION: A systemically high IL-36 level is associated with asthma severity and with both T2 and non-T2 cytokines, and it implies poor condition and enhancement of risk of AEs in asthma patients.