title: Correlation of decreased survival and IL-18 in bone metastasis.
abstract: 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.
authors.affiliation: Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume.
authors.forename: Masaki
authors.initials: M
authors.lastname: Okamoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Azuma
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
authors.forename: Haruki
authors.initials: H
authors.lastname: Imaoka
authors.forename: Jiro
authors.initials: J
authors.lastname: Ikeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Shinzo
authors.initials: S
authors.lastname: Takamori
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Edakuni
authors.forename: Seiya
authors.initials: S
authors.lastname: Kato
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Iwanaga
authors.forename: Hisamichi
authors.initials: H
authors.lastname: Aizawa
mesh_terms: 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
chemical_list: D020382:Interleukin-18; D013879:Thioredoxins; D007371:Interferon-gamma