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

Abstract

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)‐γ, granulocyte‐colony stimulating factor (G‐CSF), granulocyte‐macrophage‐colony stimulating factor (GM‐CSF), macrophage‐colony stimulating factor (M‐CSF), and tumor necrosis factor (TNF)‐α were measured by cytokine specific, enzyme‐linked immunoadsorbent assays. In addition, ratios of IL‐2, IL‐4, and IFN‐γ 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‐γ, GM‐CSF, or TNF‐α 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. Cancer 1998;83:788‐796. © 1998 American Cancer Society.

Elevated Expression of the Oncogene c-fms and Its Ligand, the Macrophage Colony-Stimulating Factor-1, in Cervical Cancer and the Role of Transforming Growth Factor-β1 in Inducing c-fms Expression

“…HPV-associated cervical cancer induces inflammatory response due to viral infection, resulting in potential increased macrophage infiltration and induction of cytokines (2,3). The presence and possible involvement of several chemokines and cytokines have been studied in cervical cancer; however, the molecular mechanisms involved in the disease process are still poorly elucidated (3).…”

“…One study found no difference in the expression of c-fms in cervical precancerous lesions and normal tissue; however, c-fms levels were not examined in cervical carcinomas (21). Several studies, one by our group, showed an increase in serum and peritoneal CSF-1 levels in cervical cancer patients compared with control (3,19,20). Combined, these studies raise an important question on whether cervical carcinomas c-fms and CSF-1 in Cervical Cancer www.aacrjournals.org express c-fms and CSF-1 and whether this expression is higher than in normal tissue.…”

“…The presence and possible involvement of several chemokines and cytokines have been studied in cervical cancer; however, the molecular mechanisms involved in the disease process are still poorly elucidated (3). One cytokine that has not been examined in much, if any, detail in reference to its involvement in cervical cancer is the macrophage colony-stimulating factor-1 (CSF-1), a cytokine and growth factor that was first identified in macrophages.…”

Pretreatment plasma levels and diagnostic utility of hematopoietic cytokines in cervical cancer or cervical intraepithelial neoplasia patients

“…These markers have been found to be capable of discriminating cervical cancer patients from those without malignant transformation. Comparable levels of these three cytokines (but without statistical significance), were observed in the study of Punnonen et al [23], although a different type of research material was used and the tested group of cervical cancer patients was much smaller (n = 23). Significant data for G-CSF has also been observed in www.fhc.viamedica.pl the studies of other authors who additionally confirmed auto -and/or paracrine growth stimulation of tumor cells by this cytokine in different histological types of cervical cancer: carcinosarcoma [24], small-cell [14] and squamous cell [11][12][13] carcinoma.…”

“…On the other hand, this data contradicts that of Punnonen et al [23] who postulated that malignant and benign tumors generally induce similar levels of cytokine production. However, these authors compared (among other gynecological malignancies) cervical cancer patients with benign ovarian and uterine lesions patients only, and purely in peritoneal fluids [23].…”