Elevated serum IL-36 subfamily levels impact on asthma control

<bold>Background:</bold> IL-36 cytokine subfamily consists of three agonists (IL-36α, IL-36β, and IL-36γ) and two antagonists (IL-36Ra and IL-38). The IL-36 subfamily was shown to be involved in the pathophysiology of various diseases, such as the upper and lower airway diseases, psoriasis and general autoimmune diseases. However, clinical contribution of the IL-36 subfamily to asthma remains unclear. <bold>Objectives:</bold> The objective of this study was to determine whether serum levels of the IL-36 subfamily were associated with clinical manifestations of asthma. <bold>Methods:</bold> This study was a cross-sectional observational study. We collected blood samples from asthmatic patients (severe n=55, non-severe n=55) and healthy volunteers (HV, n=31). Concentrations of IL-36 families in serum were measured using the ELISA (R&D Systems). Asthmatic patients were divided into the high and low IL-36 cytokine (hi- and lo-IL-36) groups. Clinical manifestations were compared between the two groups. <bold>Results:</bold> Concentrations of IL-36α, IL-36γ, and IL-36Ra were significantly elevated in asthmatic patients, especially in the severe asthmatics, compared with the HV (all p<0.05). The proportions of ACT<20 and rates of asthma exacerbation (AE) were significantly higher in the hi-IL-36γ group (hi and lo:39.5% and 20.8% for ACT, 19.3% and 3.2% for AE; p=0.01 and 0.02, respectively). Durations until first severe asthma exacerbation were significantly shorter in the hi-IL-36γ (p=0.003). <bold>Conclusions:</bold> Systemic IL-36α and IL-36γ levels are associated with disease severity in adults with asthma. Furthermore, systemic IL-36γ may affect asthma control.