Granulocyte colony-stimulating factor production by human bone marrow fibroblasts stimulated with interleukins

Granulocyte colony-stimulating factor (G-CSF) is a cytokine that mediates the clonal proliferation and differentiation of progenitor cells into mature granulocytes. The kinetics of G-CSF production by human bone marrow fibroblasts (BMF) were investigated by quantitative immunoassays. The spontaneous production of G-CSF by BMF was below the detectable level. Interleukin-1 (IL-1) induced a dose-dependent production of G-CSF, and the production reached a plateau at 50 U/ml of IL-1. G-CSF production by BMF stimulated with IL-1 was cell concentration dependent. Detectable G-CSF was produced by 5 x 10(2) BMF in a 35 x 10-mm plastic dish. The optimal range was 1 x 10(4)-5 x 10(4) BMF. Production of newly synthesized G-CSF was detectable 6 hr after stimulation and continued for approximately 48 hr. A 6-hr pulse exposure to IL-1 was necessary to induce production of G-CSF, and after 48 hr, the adherent BMF could not be restimulated. IL-2, IL-3, IL-4, IL-5, and IL-6 were unable to induce G-CSF production. However, IL-4 promoted G-CSF production after stimulation with IL-1. These results provide useful data with regard to the mechanism of G-CSF production by human BMF.