Investigation of alarmins, interleukin (IL-)23 and IL-36 sputum levels in chronic airway obstructive diseases

<b>Introduction:</b> The alarmins IL-25, IL-33 and thymic stromal lymphopoietin (TSLP) promote Th2 inflammation in asthma and could be associated with eosinophilic airway infiltration. IL-23 and IL-36 were shown to mediate the neutrophilic airway inflammation as seen in severe asthma and chronic obstructive pulmonary disease (COPD). <b>Objectives:</b> The purpose of this project was to determine the expression and the production of these cytokines from induced sputum (IS) in patients with chronic airway obstructive diseases including asthmatics and COPD. <b>Methods:</b> The alarmins, IL-23 and IL-36 concentrations were measured in IS from 20 healthy volunteers, 24 asthmatics and 20 COPD patients. The cytokines were assessed by ELISA in the IS supernatant and by RT-qPCR in the IS cells. <b>Results:</b> In the IS supernatant, only IL-23, IL-33 and IL-36 were detectable and not different between patient groups. However, when patients were classified as having an airway obstructive disease, a negative correlation was observed between IL-23 levels and VEMS % predicted (r=-0.4; p&lt;0.05). At gene level, a positive correlation between the expression of IL-23 and IL-36 was noticed (r=0.85, p&lt;0.001) and between those and the sputum neutrophil percentage (r=0.79, p&lt;0.01 and r=0.83, p&lt;0.001 respectively). In accordance, when patients were grouped by inflammatory phenotype, IL-23 and IL-36 expressions were increased in patients with neutrophilic vs eosinophilic inflammation. <b>Conclusions:</b> Our finding supports a role for local production of IL-23 and IL-36 in airway neutrophilic inflammation but not for TSLP, IL-33 and IL-25 in eosinophilic inflammation in chronic airway obstructive diseases.