Circulating IL-33 level is associated with the progression of lung cancer

Objectives: Interleukin (IL)-33 protects against infection and inflammation; however, few studies have explored the relevance of IL-33 in lung cancer patients. We evaluated relation of plasma IL-33 levels with development and progression of lung cancer. Materials and Methods: A total of 160 patients with lung cancer and 160 controls with normal lungs were enrolled. Plasma IL-33 levels were measured using a specific sandwich ELISA; these levels were followed-up in 18 patients who underwent surgery and in 14 patients treated with chemotherapy. Malignant lesions and normal lung tissues from 10 cancer patients were subjected to immunohistochemical staining for IL-33. Results: IL-33 levels were significantly lower in cancer patients than normal controls (0.08 vs. 0.38 ng/mL, p = 0.005). Among cancer patients, IL-33 decreased in a stage-dependent manner from 0.76 ng/mL in stage I patients to 0.25 ng/mL in those with stage II, 0.08 ng/mL in those with stage III, and 0.08 ng/mL in those with stage IV (p = 0.002). The levels were higher at stage I (p = 0.041) and markedly lower at stages III and IV than those of controls (p = 0.005 and p = 0.001, respectively). A similar pattern was observed when IL-33 levels were analyzed by T stage; the levels were 0.39 ng/mL at T1/T2 vs. 0.08 ng/mL at T3/T4 (p = 0.001). However, no difference was noted when stage N1 levels were compared with N2 and N3 levels (p = 0.058), or between stage MO and M1 levels (p = 0.147). IL-33 levels gradually decreased after surgical resection of malignant lesions (from 1.075 to 0.756 ng/mL, p = 0.006), but were unchanged after chemotherapy (0.705 vs. 0.829 ng/mL, p = 0.875). On immunohistochemical staining, bronchial epithelial and vascular endothelial cells of normal lung tissues mainly expressed IL-33. Conclusions: Plasma IL-33 levels are associated inversely with progression of lung cancer. The observed decreases may be attributed to lung volume reduction containing bronchial epithelium and vascular endothelium as the sources of IL-33. (C) 2015 Elsevier Ireland Ltd. All rights reserved.