Effects of lipid mediators on the synthesis of leukaemia inhibitory factor and interleukin 6 by human bone marrow stromal cells

Human bone marrow stromal cells regulate haematopoiesis by releasing cytokines such as leukaemia inhibitory factor (LIF) and interleukin 6 (IL-6), We have investigated the effects of 5 lipid mediators (i.e, 12-HETE, 15-HETE, platelet-activating factor (PAF), LTB4 and prostaglandin E-2 (PGE(2))) on their LIF and IL-6 synthesis. 12-HETE, 15-HETE and LTB4 (both at 1 mu M) stimulate the LIF production by human bone marrow stromal cells grown in 10% fetal calf serum (FCS), In contrast, PAF and PGE(2) have no effect. 12-HETE (1 mu M) enhances LIF synthesis in serum free medium 7.7-fold and stimulates IL1-induced LIF production. 12-HETE, 15-HETE, PAF and LTB4 have no effect on the spontaneous, serum- and cytokine-induced IL-6 synthesis by bone marrow stromal cells, In contrast PGE(2) significantly stimulates serum-induced IL-6 synthesis, This study reports for the first time that lipid mediators may act on human haematopoiesis by modulating LIF and IL-6 synthesis by bone marrow stromal cells. Particularly, 12-HETE enhances LIF but not IL-6 synthesis. The different regulation of IL-6 and LIF synthesis in response to lipid mediators highlights the complexity of the cytokine regulation into the human bone marrow. (C) 1998 Academic Press.