IL-6 secretion by human peritoneal mesothelial and ovarian cancer cells.
Malignant ascites of epithelial ovarian cancer patients contains high levels of interleukin 6 (IL-6). The present study was conducted to compare the secretion of IL-6 by seven different human ovarian cancer cell lines (OVCA) and cultured human peritoneal mesothelial cells (HPMC) and to examine the regulation of its production by other cytokines. IL-6 was detected in supernatant medium of all mesothelial cell cultures (8/8) and 6/7 ovarian cancer cell lines. Levels of IL-6 secreted by HPMC (median 27,100 pg/1 x 10(5) cells; range 3870-168,200) were 590-fold higher (P < 0.01) than those secreted by OVCA (median 46 pg/1 x 10(5) cells; range 0-16,450). Treatment with TNF-alpha or IL-1 beta (both 10 ng/ml) for both types of cells and both cytokines resulted in a significant (P < 0.05) elevation of IL-6 production. In OVCA IL-6 secretion was increased 7- and 39-fold and in HPMC 6- and 8-fold, respectively. Under TNF-alpha treatment IL-6-levels secreted by HPMC were 149-fold higher (P < 0.01) than those generated by OVCA. Similarly, IL-1 beta-induced IL-6 levels were 102-fold higher in HPMC (median 288,800 pg/1 x 10(5) cells; range 93,125-552,800) than in OVCA. IFN-gamma (10 ng/ml) increased IL-6 generation in OVCA (6-fold) but not HPMC. The proliferation of both cell types however, was significantly (P < 0.05) inhibited by IFN-gamma. Our results suggest that peritoneal mesothelial cells may be a prominent source of IL-6 in ovarian cancer-related ascites.