Serum and ascitic fluid levels of interleukin-1, interleukin-6, and tumor necrosis factor-alpha in patients with ovarian epithelial cancer

Abstract

Background. Recent studies have shown that multiple cytokines are secreted by ovarian epithelial cancer cells. Previous studies have shown that the cancer cell lines secrete macrophage colony‐stimulating factor (M‐CSF), granulocyte–macrophage colony‐stimulating factor (GM‐CSF), interleukin‐1 (IL‐1), interleukin‐6 (IL‐6), and transforming growth factor‐alpha (TGF‐α). Concomitantly, the serum levels of one of the growth factors (M‐CSF) was found to be significantly elevated in patients with primary ovarian cancer and in second‐look patients. The authors evaluated the serum levels of IL‐1 α, IL‐1 β, IL‐6, and tumor necrosis factor‐alpha (TNF‐α) in patients with primary ovarian epithelial cancer. These levels were then compared with cytokine concentration found in normal peritoneal fluid. Methods. Enzyme‐linked immunosorbent assay (ELISA) was used to determine the levels of cytokines in normal peritoneal fluid, ascites, and serum. Results. In serum, TNF‐α and IL‐6 were significantly increased in primary ovarian cancer patients when compared with control subjects (P < 0.0001 for both cytokines). TNF‐α and IL‐6 were also significantly higher than the levels found in second‐look patients (P < 0.007 for TNF‐α, and P = 0.0002 for IL‐6). The levels of IL‐1 α and β were not elevated in ovarian cancer. TNF‐α in the ascites was higher when compared with normal peritoneal fluid and was statistically significantly different when a cut‐off point between 71–110 pg was selected (P < 0.005). The levels of IL‐6 in ascites from patients with primary ovarian cancer also showed a marked increase (P < 0.0001) when compared with peritoneal fluid from control subjects. Conclusions. Levels of IL‐1, IL‐6, and TNF‐α were determined in normal peritoneal fluid, ovarian malignant ascites, normal serum, and serum from patients with ovarian cancer. This study showed that the patients with ovarian cancer have elevated levels of IL‐6 and TNF‐α in serum and ascitic fluid. A larger study would help in evaluating the potential use of cytokines as tumor markers in ovarian cancer.

Vascular Cell Adhesion Molecule-1 Is a Regulator of Ovarian Cancer Peritoneal Metastasis

“…The data presented here confirm a statistically significant difference in VCAM-1 protein expression on the surface of mesothelial cells from patients with ovarian cancer compared with cancer-free women. Whereas the mechanisms that regulate VCAM-1 expression in ovarian cancer patients are unknown, a known inducer of VCAM-1 expression, TNFa, is expressed by ovarian cancer cells (25) and found in malignant ascites (26). However, VCAM-1 expression was observed in patients without evidence of peritoneal metastasis (i.e., stage I or II ovarian cancer) and in regions lacking ovarian cancer.…”

Inflammatory Markers of CRP, IL6, TNFα, and Soluble TNFR2 and the Risk of Ovarian Cancer: A Meta-analysis of Prospective Studies

“…In human ovarian cancer cells, IL6 signaling was shown to regulate proliferation, adhesion, and invasion (10), and the autocrine production of TNFa stimulated the growth of ovarian cancer cell lines (11). Previous case-control studies have observed significantly higher circulating levels of these inflammatory markers in ovarian cancer cases compared with healthy controls (12,13). However, due to possible reverse causation bias, the causal roles of these markers in ovarian carcinogenesis cannot be established from retrospective studies, and these markers could be just indicators of a host response to the neoplastic process.…”

Psychosocial factors and interleukin‐6 among women with advanced ovarian cancer

“…Extreme elevations in IL-6 levels have been reported in the ascitic fluid, 8,12,29,30 and ovarian tumor cells in vitro produce substantial amounts of IL-6. 8,29 However, the extent to which the level of IL-6 in the peripheral blood reflects IL-6 in the area of the tumor is still unknown.…”