Humoral regulation of hematopoietic stem cells.

During the last two decades, studies using primarily cell culture methods disclosed that a number of hematopoietic cytokines possess stimulatory effects on primitive hematopoietic progenitors. More recently, investigators in a number of laboratories, including ours, used murine transplantation models to characterize the cytokines regulating the hematopoietic stem cells. The results are in general agreement with the cytokine interactions defined in culture. The positive cytokines may be separated into two groups: one consisting of steel factor and flt3/flt2 ligand and the other consisting of interleukin (IL)-6, IL-11, IL-12, leukemia inhibitory factor, granulocyte colony-stimulating factor (G-CSF) and thrombopoietin. Interactions of two cytokines belonging to different groups appear necessary to positively regulate the kinetics of stem cells. Surprisingly, IL-3 and IL-1 proved to have profound negative effects on hematopoietic stem cells. Studies of human hematopoietic stem cells are now necessary.