Correlation of decreased survival and IL-18 in bone metastasis.
OBJECTIVE
Previous studies have reported that serum IL-18 levels are increased in some cancers. We investigated whether IL-18 production is increased in sera and cancer cells of patients with non-small cell lung cancer (NSCLC).


METHODS
Serum levels of IFN-gamma and IL-18 and thioredoxin 1 (TRX1) were measured in 79 patients (51 males, 28 females, median age 67 years) with advanced NSCLC (57 adenocarcinoma, 22 squamous cell carcinoma; TNM stages IIIA [n=11], IIIB [n=24], and IV [n=44]) and 75 healthy age-matched controls (44 males, 31 females, median age 65 years) by enzyme-linked immunosorbent assay. We examined IL-18 production in the lungs and sites of bone metastasis of adenocarcinoma by immunohistochemistry.


RESULTS
Serum IL-18, IFN-gamma, and TRX1 levels in NSCLC patients were significantly (p<0.0001, p=0.0031, and p<0.0001, respectively) higher than in control subjects, while serum IFN-gamma levels in NSCLC were slightly increased. Serum IL-18, but not IFN-gamma or TRX1, levels were significantly (p=0.0102) and negatively associated with overall survival in NSCLC. The serum IL-18 level was identified as an independent prognostic factor for overall survival in multivariate survival analysis. Moreover, serum IL-18 levels were significantly (p=0.049) higher in NSCLC with bone metastasis than in NSCLC without bone metastasis. Based on immunohistochemistry, we observed that cancer cells in the lungs and bone metastases markedly produced IL-18.


CONCLUSIONS
Our results suggest that elevated serum IL-18 levels may be associated with IL-18 producing cancer cells in advanced NSCLC.
Okamoto
Masaki
M
Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume.
Azuma
Koichi
K
Hoshino
Tomoaki
T
Imaoka
Haruki
H
Ikeda
Jiro
J
Kinoshita
Takashi
T
Takamori
Shinzo
S
Ohshima
Koichi
K
Edakuni
Nobutaka
N
Kato
Seiya
S
Iwanaga
Tomoaki
T
Aizawa
Hisamichi
H
D000230:Adenocarcinoma / Q000097:blood / Q000401:mortality / Q000556:secondary; D000368:Aged; D001859:Bone Neoplasms / Q000097:blood* / Q000401:mortality / Q000556:secondary*; D001842:Bone and Bones / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000401:mortality / Q000556:secondary*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000097:blood; D020382:Interleukin-18 / Q000096:biosynthesis / Q000097:blood*; D007564:Japan / Q000453:epidemiology; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000097:blood* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013879:Thioredoxins / Q000097:blood
D020382:Interleukin-18; D013879:Thioredoxins; D007371:Interferon-gamma