Characterization of inhibitory activities secreted by THP-1 leukemia cells and regulation by interferon-gamma

Cells of the monocytic leukemia line, THP-1, mimic several of the functional characteristics of activated monocytes and macrophages following incubation in the tumor promoting agent, mezerein. The current paper explores the nature of the factors in medium conditioned by THP-1 cells which inhibit cell growth and the effects of interferon-gamma (IFN gamma) on their synthesis. Activity inhibiting the growth of the MDA-MB-415 mammary carcinoma line migrated in a pH range of 6.5 to 7.5 and could be resolved into 2 peaks, one corresponding to interleukin-1 beta (IL-1 beta) and the other with an apparent average molecular weight of 43 Kd. Antisera against tumor necrosis factor alpha and beta (TNF alpha and beta) and monocyte colony stimulating factor (M-CSF) had no effect on the 43 Kd inhibitor. IFN gamma enhanced the secretion of IL-1, but decreased the production of the 43 Kd inhibitor. The L-929 cell cytotoxicity assay and an ELISA were used to show that the amount of TNF alpha present was less in medium from IFN gamma treated cells. THP-1 cells also produced an IFN gamma repressed activity separating at pH 4.8 to 6.1 which inhibited the response of T cells to IL-1 in a thymocyte co-mitogenic assay. The inhibitors expressed by THP-1 cells may be comparable to the cytotoxic and cytostatic activities expressed by activated human monocytes and macrophages.