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

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.