DISTINCT AND DIRECT SYNERGISTIC EFFECTS OF IL-1 AND IL-6 ON PROLIFERATION AND DIFFERENTIATION OF PRIMITIVE MURINE HEMATOPOIETIC PROGENITOR CELLS IN-VITRO

While interleukin-1 (IL-1) and IL-6 have been demonstrated to synergiz e with colony-stimulating factors (CSFs) and stem cell factor (SCF) to stimulate myeloid colony formation of primitive hematopoietic progeni tor cells, it has not yet been established whether these effects are d irectly mediated. In the present study, direct effects of IL-1 and IL- 6 were examined on primitive Lin(-)Sca-1(+) murine bone-marrow progeni tor cells that were cultured and plated individually. IL-1 and IL-6 sh owed not only overlapping, but also distinct, patterns of direct syner gy. While IL-1 or IL-6 had no proliferative effects as single growth f actors, IL-1, in combination with granulocyte-macrophage CSF (GM-CSF), IL-3, CSF-1, and SCF, but not granulocyte-CSF (G-CSF), enhanced the c loning frequency of Lin(-)Sca-1(+) progenitors three- to five-fold, wh ereas IL-6 increased the cloning frequency in response to all four CSF s and SCF two- to seven-fold. In all cases, the size of the colonies o bserved were increased as well. Furthermore, the combined action of IL -1 and IL-6 resulted in additive or synergistic enhancement of CSF- an d SCF-stimulated colony formation of Lin(-)Sca-1(+) high proliferative potential colony-forming cells (HPP-CFCs). Finally, IL-6, but not IL- 1, enhanced the number of immature blast cells observed in CSF- and SC F-stimulated cultures.