The kinetic response of haemopoietic precursor cells, in vivo, to highly purified, recombinant interleukin-3.

Interleukin-3 is a murine haemopoietic cell growth factor which has now been prepared in recombinant form, rIL-3. This purified material has been shown to act, in vitro, in a comparable manner to the native material and has recently been shown to have an in vivo effect on the committed, in vitro colony-forming cells. We have examined the effects, in vivo, of low acute and chronic infusion doses on the pluripotent haemopoietic spleen colony-forming cells, CFU-S, (stem cells). The proliferation rate of CFU-S is rapidly increased after administration of rIL-3. This is followed by a migration of the more mature CFU-S to the spleen where, particularly under chronic rIL-3 treatment there is a large increase in CFU-S numbers. The increased proliferation of CFU-S is accompanied by increased differentiation in the form of a large increase in in vitro IL-3 responsive cells. The changes observed were not the result of endotoxin contamination in the rIL-3 preparation. Significantly, however, larger doses of lipopolysaccharide, did mimic the effects of rIL-3 in vivo. IL-3 was not detected in the blood following LPs treatment but it is suggested that LPS acts indirectly on haemopoietic precursor cells by eliciting local production of IL-3, perhaps from adjacent T cells or stromal cells.