Interleukin-1 enhances murine granulopoiesis in vivo

Interleukin-1 (IL-1), a monokine involved in host response to infection and inflammation, has recently been shown to stimulate production of granulocyte-monocyte colony-stimulating factors (CSFs) from a variety of cell types in vitro. The purpose of this study was to investigate the effects of human IL-1 on granulopoiesis in vivo. CF1 female mice were injected with a single dose of either highly purified human IL-1 or recombinant human IL-1 alpha (rIL-1 alpha). Heat-inactivated IL-1 or rIL-1 alpha served as controls. Physiologic doses of the IL-1 preparations were initially established by evaluating neutrophil egress from bone marrow (BM). Significant peripheral neutrophilia developed 3 h after injection of 10 U (doubling units) purified IL-1, in association with decreased marrow neutrophils. Significant neutrophilia occurred 6 h after injection of 5 x 10(3) U (half-maximal units) rIL-1 alpha. Serum colony-stimulating activity (CSA) and BM colony formation (CFU-GM) were subsequently measured in standard agar culture at various times following injection. A significant rise in CSA occurred between 3 and 6 h after injection of purified IL-1, and a significant increase in BM CFU-GM developed 48 h after injection. Similar increases in CSA and CFU-GM occurred following injection of rIL-1 alpha. These results suggest that IL-1 may play an important role in the regulation of granulopoiesis in vivo by enhancing the production of CSFs required for myeloid proliferation.