Preoperative serum interleukin-18 level as a postoperative prognostic marker in patients with gastric carcinoma.
BACKGROUND
Interleukin-18 (IL-18), a recently described cytokine produced mainly by macrophages, stimulates interferon-gamma (IFN-gamma) production by natural killer cells and T cells. Although it has been reported that serum IL-18 levels are higher in patients with advanced tuberculosis and acute graft-versus-host disease compared with normal controls, the authors found no reports regarding serum IL-18 levels in patients with malignant solid tumors. The purpose of this study was to determine serum IL-18 levels and their clinical significance in patients with gastric carcinoma.


METHODS
Peripheral blood samples were obtained from 94 patients with gastric carcinoma who underwent curative surgery and from 50 healthy volunteers. The serum IL-18 level, the IFN-gamma, level, and the Helicobacter pylori (HP) serology status were determined in each sample with an enzyme-linked immunosorbent assay.


RESULTS
The mean serum IL-18 level for all patients was significantly higher compared with the mean level in healthy volunteers (P < 0.01). IFN-gamma titers were below the level of detection in all samples tested. When the patients were subdivided into groups, it was found that the serum IL-18 level in patients with Stage II and III disease was significantly higher compared with the level found in healthy volunteers (P < 0.01). The serum IL-18 level decreased after patients underwent surgical resection. However, there was no significant difference in the serum IL-18 level between healthy controls and patients with Stage I or IV disease. Patients with IL-18 levels >or= 310 pg/mL (i.e., equal to or greater than the mean levels +/- 1 standard deviation in the healthy volunteers) experienced a significantly lower survival rate compared with patients who had IL-18 levels < 310 pg/mL after undergoing surgery (P < 0.05) despite a lack of any discernible difference in clinicopathologic factors between the two groups. The serum IL-18 level was identified as an independent postoperative prognostic factor in multivariate survival analysis using a Cox proportional hazards model (hazard ratio, 4.89; P = 0.01). There was no significant correlation between HP serology status and serum IL-18 levels.


CONCLUSIONS
The preoperative serum IL-18 level may represent a significant postoperative prognostic determinant in patients with gastric carcinoma. Its function in the host immune system remains to be elucidated.
Kawabata
T
T
Department of Surgery I, National Defense Medical College, Tokorozawa, Japan. srg1717@gr.ndmc.ac.jp
Ichikura
T
T
Majima
T
T
Seki
S
S
Chochi
K
K
Takayama
E
E
Hiraide
H
H
Mochizuki
H
H
D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005743:Gastrectomy; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
D000907:Antibodies, Bacterial; D015415:Biomarkers; D020382:Interleukin-18; D007371:Interferon-gamma