HOST-TUMOR INTERACTION IN OVARIAN-CANCER - SPONTANEOUS RELEASE OF TUMOR-NECROSIS-FACTOR AND INTERLEUKIN-1 INHIBITORS BY PURIFIED CELL-POPULATIONS FROM HUMAN OVARIAN-CARCINOMA IN-VITRO

The biological activity of tumor necrosis factor (TNF alpha/beta) and interleukin-1 beta (IL-1 beta) can be blocked by soluble, naturally oc curring molecules-TNF alpha/beta binding proteins (BP-55 and BP-75), d erived from the extracellular portion of the 55- and 75-kDa TNF alpha/ beta membrane receptors, and IL-1 receptor antagonist (IL-1ra), respec tively. We examined the levels of these cytokines and their inhibitors in cell-free ascites of 18 patients with advanced ovarian carcinoma b y ELISA. Levels of both TNF BP and IL-1ra dramatically exceeded those of TNF and IL-1; thus, it is unlikely that these cytokines are active in ascites from patients with this disease. We then elutriated solid t umor samples from three additional patients, yielding pure populations of tumor cells, macrophages, and lymphocytes. Cells were cultured for up to 48 hr and the spontaneous production of TNF, IL-1, and their in hibitors was measured by ELISA. Tumor cells and macrophages both relea sed inhibitors for TNF and IL-1. Tumor cells released IL-1ra and BP-55 , while macrophages released IL-1ra and BP-75. Kinetic studies showed that both tumor cells and macrophages produced an initial burst of TNF alpha and IL-1 beta which was overtaken within 48 hr by a sustained p roduction of TNF BP and IL-1ra. Lymphocytes released no TNF alpha or T NF beta, which alone suggests that tumor associated lymphocytes are lo cally quiescent in vivo. TNF and IL-1 inhibitors originate from tumor cells and tumor associated macrophages and probably block TNF and IL-1 activity locally and regionally in ovarian carcinoma patients. Whethe r this phenomenon contributes to the pathogenesis of this disease rema ins to be determined. (C) 1994 Academic Press, Inc.