SPONTANEOUS RELEASE OF INTERLEUKIN-6 BY PRIMARY CULTURES OF LYMPHOID AND TUMOR-CELL POPULATIONS PURIFIED FROM HUMAN OVARIAN-CARCINOMA

Interleukin-6 (IL-6) is a cytokine that has been implicated as a growt h factor in human ovarian carcinoma, yet the in vivo source of IL-6 in patients remains undefined. We measured IL-6 by ELISA in cell-free as cites (CFA) of 19 patients with ovarian carcinoma, IL-6 was detectable in all samples (mean level 3.3 ng/mI). To identify the cellular sourc e of IL-6, we measured this cytokine by ELISA in 24-48 h supernatants of cultured lymphocyte-, macrophage-, and tumor cell-enriched populati ons purified from three solid ovarian carcinomas by centrifugal elutri ation. All cell populations spontaneously released IL-6; however, tumo r eel and tumor-associated macrophage released levels of IL-6 that gre atly exceeded those released by tumor-associated lymphocytes. Kinetic studies revealed that IL-6 was detectable at 6 h and that levels incre ased in all cultures examined over a 48 h time course. These data sugg est that both tumor and infiltrating host cells may be the source of t he high levels of IL-6 found in carcinomatous ascites. Furthermore, al though all three cell types examined may contribute to IL-6 production in patients with ovarian carcinoma, tumor cells are perhaps the most clinically significant source.