Interleukin-1 alpha enhances the in vitro survival of purified murine granulocyte-macrophage progenitor cells in the absence of colony- stimulating factors

Interleukin-1 (IL-1), recently identified as hemopoietin-1, affects hematopoiesis by presumably direct and indirect mechanisms. IL-1 stimulates primitive hematopoietic stem cells to express receptors for the granulocyte-macrophage colony-stimulating factors (GM-CSFs) and stimulates CSF release from accessory cells. We used highly purified murine granulocyte-macrophage progenitor cells (CFU-GM, up to 92% cloning efficiency) to assess the effects of IL-1 alpha on the proliferation, differentiation, and survival of these cells. The results demonstrated that IL-1 alpha does not directly influence the proliferation or differentiation of purified CFU-GM in the presence of plateau concentrations of purified natural or recombinant CSFs, and IL- 1 alpha lacks intrinsic CSF activity of its own. CSF deprivation studies showed that IL-1 alpha rapidly (within one hour) promoted CFU- GM survival in the absence of CSF. This enhanced survival stimulated by IL-1 alpha was observed with CFU-GM responding to purified recombinant GM-CSF, natural M-CSF, recombinant G-CSF, recombinant IL-3, or IL-3 in WEHI-conditioned medium, and no effect on the pattern of CFU-GM differentiation occurred in cultures incubated with IL-1 alpha in the absence of CSF. The IL-1 alpha effects on CFU-GM are probably due to a direct action on progenitor cells because the presence or absence of accessory cells did not alter the results and concentrations of the CSFs that were too low to stimulate the proliferation of CFU-GM could not mimic the IL-1 alpha effect on CFU-GM survival.