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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

  • Author(s): Burger, RA
  • Grosen, EA
  • Ioli, GR
  • Van Eden, ME
  • Brightbill, HD
  • Gatanaga, M
  • DiSaia, PJ
  • Granger, GA
  • Gatanaga, T
  • et al.
Abstract

The biological activity of tumor necrosis factor (TNFα/β) and interleukin-1β (IL-1β) can be blocked by soluble, naturally occurring molecules-TNFα/β binding proteins (BP-55 and BP-75), derived from the extracellular portion of the 55- and 75-kDa TNFα/β membrane receptors, and IL-1 receptor antagonist (IL-1ra), respectively. We examined the levels of these cytokines and their inhibitors in cell-free ascites of 18 patients with advanced ovarian carcinoma by 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 tumor 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 inhibitors was measured by ELISA. Tumor cells and macrophages both released 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 TNFα and IL-1β which was overtaken within 48 hr by a sustained production of TNF BP and IL-1ra. Lymphocytes released no TNFα or TNFβ, which alone suggests that tumor associated lymphocytes are locally 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. Whether this phenomenon contributes to the pathogenesis of this disease remains to be determined. © 1994 Academic Press, Inc.

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