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


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 M0 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.
Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Gumi-Si, Gyeongsangbuk-Do, Republic of Korea. Electronic address: g72264@schmc.ac.kr.
Myung Shin
MS
Kim
Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea. Electronic address: kes0126@naver.com.
Eunsom
E
Kim
Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Wonmi-gu, Bucheon, Gyeonggi-do 420-767, Republic of Korea. Electronic address: huccine@naver.com.
Jeong-Seok
JS
Heo
Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Wonmi-gu, Bucheon, Gyeonggi-do 420-767, Republic of Korea. Electronic address: dnwls75@naver.com.
Da-Jeong
DJ
Bae
Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Wonmi-gu, Bucheon, Gyeonggi-do 420-767, Republic of Korea. Electronic address: lajoal@nate.com.
Jong-Uk Wook
JU
Lee
Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Wonmi-gu, Bucheon, Gyeonggi-do 420-767, Republic of Korea. Electronic address: halamadrid@naver.com.
Tae-Hyeong
TH
Lee
Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Wonmi-gu, Bucheon, Gyeonggi-do 420-767, Republic of Korea. Electronic address: 1204thgml@naver.com.
Hyeon Ju
HJ
Lee
Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Wonmi-gu, Bucheon, Gyeonggi-do 420-767, Republic of Korea. Electronic address: hschang@sch.ac.kr.
Hun Soo
HS
Chang
Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-Do, Republic of Korea. Electronic address: js1221@schmc.ac.kr.
Jong Sook
JS
Park
Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-Do, Republic of Korea. Electronic address: jas877@schmc.ac.kr.
An Soo
AS
Jang
Departmentof Anatomic Pathology, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-Do, Republic of Korea. Electronic address: eskamd@schmc.ac.kr.
Eun Suk
ES
Koh
Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Gumi-Si, Gyeongsangbuk-Do, Republic of Korea. Electronic address: hwangpark@schmc.ac.kr.
Hun Gyu
HG
Hwang
Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Gumi-Si, Gyeongsangbuk-Do, Republic of Korea. Electronic address: guneil@schmc.ac.kr.
Guneil
G
Lim
Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea. Electronic address: soohyun@konkuk.ac.kr.
Soohyun
S
Kim
Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-Do, Republic of Korea. Electronic address: mdcspark@hanmail.net.
Choon-Sik
CS
Park
D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D000067596:Interleukin-33 / Q000097:blood*; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D011013:Pneumonectomy / Q000379:methods
C506536:IL33 protein, human; D000067596:Interleukin-33
Chemotherapy; Interleukin-33; Lung cancer; Plasma; Stage; Surgery