Elevated sputum IL-36 levels are associated with neutrophil-related inflammation in COPD patients

Background Interleukin (IL)-36, including IL-36 alpha, IL-36 beta, and IL-36 gamma in the IL-1 family, are agonists of their receptors. IL-36 expression is associated with inflammation, including lung infection in humans. However, there is no information on its role in the inflammation of different types of chronic obstructive pulmonary disease (COPD). Objective This study focused on the sputum IL-36 alpha, IL-36 beta, and IL-36 gamma levels in stable COPD patients and their relationship with lung function and other cytokines in different inflammatory types of COPD patients. Methods Sputum specimens were collected from 73 stable COPD patients and 20 age- and gender-matched healthy controls. The levels of sputum IL-36 alpha, IL-36 beta, and IL-36 gamma and other cytokines were quantified and sputum cells were characterized. The potential relationship between the levels of sputum IL-36 alpha, IL-36 beta, or IL-36 gamma and lung functional measures, inflammatory cells, and cytokines was analyzed. Results In comparison with the healthy controls, sputum IL-36 alpha and IL-36 gamma levels significantly increased in COPD (106.8 pg/mL vs. 76.9 pg/mL P =.001, 397.9 pg/mL vs. 359.5 pg/mL P =.006). The sputum IL-36 alpha and IL-36 gamma levels were significantly higher in the neutrophilic and mixed granulocytic types than that in the eosinophilic and paucigranulocytic types of COPD patients. The sputum IL-36 alpha levels were positively correlated with sputum IL-36 gamma levels and the numbers of sputum neutrophils, and the sputum IL-36 gamma levels were positively correlated with the numbers of sputum lymphocytes in COPD patients. Conclusions Elevated levels of sputum IL-36 alpha and IL-36 gamma were detected in COPD patients and may provide insights into the inflammatory pathways in neutrophilic COPD.