Cytokine production profiles in the peritoneal fluids of patients with malignant or benign gynecologic tumors.

BACKGROUND

Cytokines play a key role in the regulation of cells of the immune system and also have been implicated in the pathogenesis of malignant diseases. Some cytokines have been shown to have potential in the diagnosis of cancer.

METHODS

A total of 111 patients with ovarian, cervical, or endometrial carcinomas or benign ovarian or uterine tumors were enrolled on the study, and the levels of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-gamma, granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage-colony stimulating factor (GM-CSF), macrophage-colony stimulating factor (M-CSF), and tumor necrosis factor (TNF)-alpha were measured by cytokine specific, enzyme-linked immunoadsorbent assays. In addition, ratios of IL-2, IL-4, and IFN-gamma production were studied to characterize the type of T-cell response that occurred in the peritoneal cavities of the patients.

RESULTS

High levels of M-CSF (mean for all patients, 26,050 pg/mL) and G-CSF (mean for all patients, 20,267 pg/mL) were observed in virtually all patients, but no significant differences between the study groups were observed. Similarly, no differences in the levels of IL-2, IL-4, IL-10, IFN-gamma, GM-CSF, or TNF-alpha were found. However, IL-6 levels were significantly higher in patients with ovarian carcinoma (mean +/- standard error of the mean [SEM]: 5572 +/- 1266) or benign tumors (mean +/- SEM: 4474 +/- 2008) than in those with cervical (mean +/- SEM: 1222 +/- 546) or endometrial carcinoma (mean +/- SEM: 1977 +/- 616). A predominantly Th1 type cytokine profile, irrespective of the diagnosis, was observed in patients with gynecologic tumors.

CONCLUSIONS

With the exception of IL-6, the cytokine synthesis profiles in the peritoneal fluids of patients with benign and malignant gynecologic tumors were found to be similar. These results suggest that cytokine production in these patients is a result of nonspecific inflammation rather than a specific response against the tumor cells, and that skewing of cytokine synthesis toward either the Th1 or the Th2 phenotype is not the underlying mechanism resulting in the malignant process in women with gynecologic tumors.