Interleukin-1 induces human bone marrow-derived fibroblasts to produce multilineage hematopoietic growth factors.

Interleukin-1 (IL-1) has been shown to induce stromal cells, including endothelial cells and fibroblasts, to produce multilineage hematopoietic growth factors. Although both of these cell types are well-described elements of the hematopoietic microenvironment, previous studies of IL-1-inducible colony-stimulating factor responses have utilized fibroblasts and endothelial cells from nonhematopoietic sites. Since we hypothesize that this intercellular growth network is active in the hematopoietic microenvironment, we sought to determine the responsiveness of bone marrow fibroblasts to IL-1. We demonstrate here that recombinant human IL-1 alpha and beta stimulate the dose-dependent release of granulocyte-macrophage colony-stimulating activity (GM-CSA) and burst-promoting activity (BPA) by cultured human bone marrow fibroblasts. We conclude that bone marrow fibroblasts produce hematopoietic growth factors in response to interleukin-1, and that this may be a mechanism by which stromal cells regulate cellular growth and differentiation within the hematopoietic microenvironment.