Murine B‐cell stimulatory factor‐1 (BSF‐1)/Interleukin‐4 (IL‐4) is a multilineage colony‐stimulating factor that acts directly on primitive hemopoietic progenitors

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Abstract
Interleukin‐4 (IL‐4), which was originally identified as a B‐cell growth factor, has been shown to produce diverse effects on hemopoietic progenitors. The present study investigated the effects of purified recombinant murine IL‐4 on early hemopoetic progenitors in methylcellulose culture. IL‐4 supported the formation of blast cell colonies and small granulocyte/macrophage (GM) colonies in cultures of marrow and spleen cells of normal mice as well as spleen cells of mice treated with 150 mg/kg 5‐fluorouracil (5‐FU) 4 days earlier. When the blast cell colonies were individually picked and replated in cultures containing WEHI‐3 conditioned medium and erythropoietin (Ep), a variety of colonies were seen, including mixed erythroid colonies, indicating the multipotent nature of the blast cell colonies supported by IL‐4. To test whether or not IL‐4 affects multipotent progenitors directly, we replated pooled blast cells in cultures under varying conditions. In the presence of Ep, both IL‐3 and IL‐4 supported a similar number of granulocyte/erythrocyte/macrophage/megakaryocyte (GEMM) colonies. However, the number of GM colonies supported by IL‐4 was significantly smaller than that supported by IL‐3. When colony‐supporting abilities of IL‐4 and IL‐3 were compared using day‐4 post‐5‐FU spleen and day‐2 post‐5‐FU marrow cells, IL‐4 supported the formation of fewer blast cell colonies than did IL‐3. IL‐4 and IL‐6 revealed synergy in support of colony formation from day 2 post‐5‐FU marrow cells. These results indicate that murine IL‐4 is another direct‐acting multilineage colonystimulating factor (multi‐CSF), similar to IL‐3, that acts on primitive hemopoietic progenitors.

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