Interleukin-4--a dual regulatory factor in hematopoiesis

Interleukin-4/B-cell stimulatory factor-1 (IL-4/BSF-1) is a unique cytokine which may have multiple regulatory functions in vitro and in vivo. It has been shown to produce diverse effects on hematopoietic progenitors and can act on the proliferation and differentiation of committed as well as primitive hematopoietic progenitors. It acts synergistically with G-CSF to support neutrophil colony formation. In contrast, it inhibits IL-3-dependent colony formation and macrophage colony formation supported by IL-3 plus M-CSF, GM-CSF, or by M-CSF alone. It also suppresses pure and mixed megakaryocyte colony formation supported by IL-3 in the presence of Erythropoietin (EPO). IL-4, however, supports multipotential blast cell colony formation. And there are apparent differences between the functions of IL-4 and IL-3. IL-4 is able to exert its hematopoietic actions directly and indirectly. For example, it enhances the release of GM-CSF or G-CSF from T-lymphocytes and TNF-alpha from monocytes. Since IL-4 receptors have been shown to be expressed on bone marrow stromal cells as well as hematopoietic cells, it may also act in the bone marrow microenvironment. These results suggest that IL-4 is an intermediate-acting, lineage-non-specific factor just like IL-3 or GM-CSF. Complex interactions between many cytokines including IL-4 may act in the regulation of normal as well as pathological hematopoiesis.