TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-6 ARE DIFFERENTLY EXPRESSED BY FRESH HUMAN CANCEROUS OVARIAN TISSUE AND PRIMARY-CELL LINES

The expression levels of tumor necrosis factor-alpha (TNF-alpha) and i nterleukin-6 (IL-6) were evaluated in normal and cancerous ovarian tis sue and primary cell lines (PCL), Seven normal and 10 cancerous, forma lin-fixed ovarian samples were examined for TNF-alpha and IL-6 express ion by immunohistochemical staining using polyclonal rabbit anti-human TNF-alpha and IL-6 antibodies. Fresh normal and cancerous specimens w ere also examined for TNF-alpha and IL-6 secretion by bioassay and imm unoassay prior to and following in vitro stimulation with lipopolysacc haride (LPS). The levels of IL-6 and TNF-alpha were higher in cancerou s tissues than in normal specimens. In vitro stimulation of normal and cancerous ovarian tissues and PCL revealed their capacity to secrete IL-6. Cancerous tissue and PCL secreted higher levels than normal tiss ue and PCL. Stimulation of both groups with LPS increased their capaci ty to secrete IL-6. Optimal secretion of IL-6 by the cancerous tissue was observed after 72 hours with or without LPS (10 mu g/ml), Normal t issue secreted maximal levels of IL-6 after 96 hours with or without L PS. PCL from normal ovarian tissue secreted IL-6 constitutively and op timal expression was detected after 96 hours. Carcinoma PCL from cance rous ovarian tissue demonstrated optimal secretion of IL-6 after 24 ho urs. Stimulation of both types of cells with LPS, IL-1 or TNF-alpha, i ncreased their capacity to secrete IL-6, TNF-alpha activity was detect ed in vitro only in supernatants of ovarian cancerous tissue and only after LPS stimulation; optimal levels were detected after 48 hours and 1 mu g/ml LPS. Our results indicate that IL-6 and TNF-alpha are expre ssed in cancerous ovarian tissue at a higher level than in normal ovar ian tissues. Carcinoma cells of ovarian tissues are the main cellular source of these cytokines. The conditions controlling the secretion of these cytokines? under irt vitro conditions, are different in cancero us and normal ovarian tissues.