EFFECT OF BIOLOGICAL RESPONSE MODIFIERS ON CYTOKINE PRODUCTION IN A DIFFERENTIATING HUMAN MYELOGENOUS LEUKEMIC CELL LINE

Abstract

Natural biological response modifiers such as lignin, tannin, and protein-bound polysaccharide (PSK) stimulate the production of tumor necrosis factor (TNF), interleukin-1α (IL-1α), and IL-1β by cultured human peripheral blood mononuclear cells. However, these agents induce no detectable amount of these cytokines in cultured human skin fibroblast, stomach cell carcinoma, renal cell carcinoma, glioma, glioblastoma, or myelogenous leukemic cell lines. When human myelogenous leukemic cell lines (ML-1, THP-1, HL-60) were treated with 12-O-tetradecanoylphorbol 13-acetate (TPA), they were differentiated into adherent macrophages expressing higher NBT-reducing activity, but only ML-1 cells became IL-1β producing cells. If ML-1 cells were sequentially treated with TPA and then PSK, further increase of IL-1β production was observed. When HL-60 cells were treated with vitamin Ds, another monocyte/macrophage inducer, their NBT-reducing activity was significantly increased, without induction of IL-1β production. These data suggest that (i) the types of differentiation-associated properties expressed might be determined by the inducers, (ii) the cytokine production might be stimulated via direct action of the inducers or a secondary result of differentiation induction, and (iii) the expression of conventional differentiation markers does not necessarily reflect mature cell functions.