Introduction

The term aplastic anemia (AA) encompasses a group of stem-cell disorders characterized by peripheral-blood pancytopenia and hypocellular bone marrow. Although the exact mechanisms responsible for its pathogenesis are unknown, possible causes include a primary stem-cell defect, immune-mediated inhibition of hemopoiesis, and an abnormal bone marrow microenvironment (Camitta et al; 1982; Young and Maciejewski, 1997). Normal hemopoiesis is sustained by interactions between hemopoietic stem cells, cells of the bone marrow microenvironment, and cytokines produced by these cells. These cytokines are essential for the viability, proliferation, and differentiation of hemopoietic stem cells. In vitro evidence for the existence of a supporting microenvironment in hemopoiesis comes from the development of a long-term bone marrow culture (LTBMC) system (Dexter et al., 1977; Gartner and Kaplan, 1980). LTBMC is composed of confluent layers of marrow-adherent cells including fibroblasts, endothelial cells, adipocytes, and macrophages. LTBMC forms an in vitro model of the bone marrow microenvironment. Marrow stromal cells are thought to exert their regulatory role in hemopoiesis, at least in part, by the production of certain cytokines. Monolayer cultures of marrow-adherent cells have been shown to produce a variety of cytokines including granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), and stem cell factor (SCF), either constitutively or after stimulation by interleukin-1 (IL-1) or tumor necrosis factor-α (TNF-α) (Kaushansky et al., 1988; Linenberger et al., 1995; Schadduk et al., 1983).

Several earlier studies showed elevated circulating levels of colony-stimulating activity in patients with AA (Nissen et al., 1985; Yen et al., 1985).