Effect of cytokines and lipid mediators on the synthesis of interleukin 1 beta by human bone marrow stromal cells

This study investigates the production of interleukin (IL-)1 beta by cultur ed human bone marrow stromal cells. RT-PCR experiments indicate that two-th irds of cultures constitutively express IL-1 beta mRNA transcripts. Their c ell-associated IL-1 beta levels are elevated after stimulation with tumour necrosis factor (TNF-)alpha but not with cytokines such as IL-1 alpha, IL-3 , IL-4, IL,-6, IL-7, IL-10, SCF, G-CSP, M-CSP and TGF-beta or lipid mediato rs such as PGE(2), LTB4, LXA(4), LXB4, 12-HETE, 15-HETE and PAF. Addition o f IL-4, but not IL-10 or TGF-beta, reduces the TNF-alpha-induced cell-assoc iated IL-1 beta, IL-1 beta is never detected in bone marrow stromal cell su pernatants whatever the stimulant added. In conclusion the pro-inflammatory molecule TNF-alpha stimulates bone marrow stromal cell-associated IL-1 bet a levels while the anti-inflammatory cytokine IL-3 reduces the TNF-alpha-in duced effect. These results strengthen the key regulatory role of IL-4 on t he production of haematopoietic cytokines by human bone marrow stromal cell s, (C) 2000 Academic Press.