Inhibition of cell proliferation by interleukin-1 derived from monocytic leukemia cells

Growth inhibitors and interleukin-1 (IL-1) are two biological response modifiers produced by mezerein-treated THP-1 cells maintained in serum-free medium. The activities comigrated with isoelectrofocusing in a pH range of 6.7 to 7.3. Subsequent molecular sieving on an AcA-54 column revealed that a portion of the growth-inhibitory activity for the mammary cell line MCF-7 remained associated with IL-1. IL-1-containing fractions were further analyzed by chromatography with DEAE-Sephacel, phenyl:Sepharose, and concanavalin A:Sepharose. In each instance, IL-1 coeluted with growth-inhibitory activity. IL-1 and growth-inhibitory activities partially purified by sequential isofocusing, AcA-54 chromatography, and DEAE-Sephacel were located in a single region following preparative polyacrylamide gel electrophoresis. Elution, concentration, and analytical polyacrylamide gel electrophoresis of this region resulted in a single band with an apparent molecular weight of 17,000. Stability studies revealed similarities between the IL-1 activity and growth-inhibitory activity in their sensitivity to a variety of physical and chemical treatments. A commercial source of human IL-1 also inhibited the growth of MCF-7 cells. DEAE-purified IL-1 derived from THP-1 cells inhibited the growth of 7 of 11 cell types tested, and all inhibited cell lines were established from malignant sources. Prostaglandin synthesis by MCF-7 cells in response to IL-1 was not responsible for growth inhibition.