Preoperative serum interleukin-18 level as a postoperative prognostic marker in patients with gastric carcinoma

Abstract

BACKGROUND Interleukin‐18 (IL‐18), a recently described cytokine produced mainly by macrophages, stimulates interferon‐γ (IFN‐γ) 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‐γ, 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‐γ 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 ≥ 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. Cancer 2001;92:2050–5. © 2001 American Cancer Society.

Correlation of Decreased Survival and IL-18 in Bone Metastasis

“…Previous studies have reported that serum IL-18 levels are elevated in patients with some cancers (18,19). High serum IL-18 levels are also observed in breast cancer patients with bone metastases (27) (28).…”

Expression and significance of intratumoral interleukin-12 and interleukin-18 in human gastric carcinoma

“…Merendino et al [12] reported that serum IL-18 level was significantly higher in breast cancer patients with liver or bone metastases than in patients without metastasis or healthy individuals, implying that IL-18 could be regard as a metastatic marker for breast cancer, irrespective of its biological activities. The preoperative serum IL-18 level may represent a significant postoperative prognostic determinant in patients with gastric carcinoma, and patients with IL-18 levels over 310 pg/mL experienced a significantly lower survival rate after surgery than under 310 pg/mL [13] . IL-18 could significantly increase MMP-9 production at both mRNA and protein levels [14] , thus enhancing the aggressiveness of malignant tumors, facilitating cancer metastasis through the induction of vascular cell adhesion molecule-1 (VCAM-1), and promoting cancer cell adhesion and liver metastasis in vivo [15] .…”

Vaccine-Induced Immunity againstHelicobacter pyloriInfection Is Impaired in IL-18-Deficient Mice

“…In Helicobacter-infected individuals, IL-18 mRNA expression was increased in the gastric mucosa (41,42). The serum IL-18 level was significantly increased in patients with gastric carcinoma, which is frequently found to be associated with H. pylori infection (2,43). Moreover, a limited study in mice addressing the role of IL-18 found no difference in resistance to infection between immunized IL-18 Ϫ/Ϫ and wild-type (WT) 3 mice (44).…”