The hematopoietic microenvironment in the elderly: defects in IL-1-induced CSF expression in vitro

The expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) genes by stromal cells of the hematopoietic microenvironment is regulated, in vitro, by interleukin 1 alpha (IL-1 alpha) and IL-1 beta. We reasoned that malfunction of this inductive mechanism in vivo might contribute to the intolerance of the aged to myelosuppressive therapy. We found that bone marrow fibroblasts from healthy elderly (ages 65-75 years) volunteers were less sensitive to the inductive effects of recombinant IL-1 beta than were marrow fibroblasts from younger volunteers, and we proposed that an age-related decline in sensitivity of marrow stroma to IL-1 may impair the ability of the elderly to increase production of hematopoietic growth factors under conditions of physiologic stress.