EFFECT OF CYTOKINES AND LIPID MEDIATORS ON THE SYNTHESIS OF INTERLEUKIN 1β BY HUMAN BONE MARROW STROMAL CELLS

This study investigates the production of interleukin (IL-)1β by cultured human bone marrow stromal cells. RT-PCR experiments indicate that two-thirds of cultures constitutively express IL-1β mRNA transcripts. Their cell-associated IL-1β levels are elevated after stimulation with tumour necrosis factor (TNF-)α but not with cytokines such as IL-1α, IL-3, IL-4, IL-6, IL-7, IL-10, SCF, G-CSF, M-CSF and TGF-β or lipid mediators such as PGE2, LTB4, LXA4, LXB4, 12-HETE, 15-HETE and PAF. Addition of IL-4, but not IL-10 or TGF-β, reduces the TNF-α-induced cell-associated IL-1β. IL-1β is never detected in bone marrow stromal cell supernatants whatever the stimulant added. In conclusion the pro-inflammatory molecule TNF-α stimulates bone marrow stromal cell-associated IL-1β levels while the anti-inflammatory cytokine IL-4 reduces the TNF-α-induced effect. These results strengthen the key regulatory role of IL-4 on the production of haematopoietic cytokines by human bone marrow stromal cells.