Cytokine profile in Indian women with cervical intraepithelial neoplasia and cancer cervix

Abstract

Cervical cancer develops from the preneoplastic cervical intraepithelial neoplasia (CIN). Host factors are critical in regulating tumor growth and cytokines, which modulate immunologic control may be of particular importance. The objective of this study was to assess the production of cytokines by peripheral blood mononuclear cells (PBMCs) in Indian women with cancer cervix and CIN. Sixty patients with cancer cervix (including all FIGO stage I-IV), 35 patients with CIN, and 30 healthy controls were enrolled in this study. The human papillomavirus (HPV) 16 and 18 status was determined in all the study groups. The PBMC culture supernatant was collected for cytokine estimations by enzyme-linked immunosorbent assay (interleukin-2 [IL-2], interferon-gamma [IFN-gamma], interleukin-4 [IL-4], and interleukin-10 [IL-10]). IL-2 levels showed a significant decline in high-grade CIN and cancer patients, whereas IFN-gamma levels were decreased only in patients with advanced cancer cervix. An increase in the levels of IL-4 and IL-10 was found in all cancer cervix and CIN grade III patients, as compared to those with early CIN grades and healthy controls. The cytokine ratios decreased significantly (P < 0.001 for all the ratios), when cervical cancer patients were compared with controls and CIN cases. The type 2 and type 1 cytokine levels were significantly correlated (P < 0.000) with HPV status. We conclude that a pronounced shift from type 1 to type 2 cytokine production is associated with more severe disease. These data reinforce the need for detailed analysis of immune dysregulation in CIN and cancer cervix patients.

IL-10 Promotes Tumor Aggressiveness via Upregulation of CIP2A Transcription in Lung Adenocarcinoma

“…The upregulated secretion of IL-10 may inhibit immune response against HPV infection in early cervical lesions. Reports have shown that higher IL-10 could be detected in plasma of patients with CIN III and with carcinoma than in patients with CIN I and CIN II (11)(12)(13). Moreover, patients suffering from cervical cancer show higher IL-10 expression in HPV16-positive tumors than in HPV16-negative tumors, which again indicates an association between IL-10 and the carcinogenesis of HPV-associated cancer (14).…”

“…HPV infection is a major etiologic factor in cervical carcinogenesis. IL-10 mRNA levels in cervical intraepithelial neoplasia (CIN) were significantly higher compared with normal cervical tissues (11)(12)(13). The upregulated secretion of IL-10 may inhibit immune response against HPV infection in early cervical lesions.…”

The paradox of IL-10-mediated modulation in cervical cancer

“…An increased number of IL-10-positive cells was detected in the cervix of patients with cervical intraepithelial neoplasia (CIN), associated with the grades of dysplasia (15). Furthermore, an increase in the levels of IL-10 was observed in cervical cancer and CIN grade III patients, compared to those with early CIN grades and healthy controls (16). The genotype predisposing to the production of high levels of IL-10 is more commonly observed in cervical cancer patients, compared to healthy women (17).…”

Serum levels of soluble interleukin-2 receptor in association with oxidative stress index in patients with different types of HPV

“…Many of the authors have evaluated immune markers that were locally secreted in the cervix, tissue-based immune markers or immune response by patient-derived peripheral blood mononuclear cells (PBMCs) [27][28][29][30]. However, data concerning infection-related immune response in either plasma or serum is limited.…”