Transforming growth factor‐β1 enhances the suppression of human hematopoiesis by tumor necrosis factor‐α or recombinant interferon‐α

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Abstract
The effects of transforming growth factor-β1 (TGF-β1) on human hematopoiesis were evaluated in combination with two other regulatory cytokines, namely, recombinant human tumor necrosis factor-α (TNF-α) and recombinant human interferon-α (rIFN-α). Combinations of TNF-α and TGF-β1 resulted in a synergistic suppression of colony formation by erythroid progenitor cells (BFU-E) and an additive suppression of granulocyte-macrophage (CFU-GM) and multipotential (CFU-GEMM) progenitor cells. In addition, TGF-β1 synergized with rIFN-α to suppress CFU-GM formation, while the combined suppressive effects of both cytokines on CFU-GEMM and BFU-E were additive. When TGF-β1 was tested with TNF-α or IFN-α on granulocyte/macrophage colony-stimulating factor (GM-CSF)-stimulated bone marrow cells in a 5-day proliferation assay, the antiproliferative effects of TGF-β1 and TNF-α were additive, while those with TGF-β1 and rIFN-α were synergistic. A similar pattern was seen in the suppression of the myeloblastic cell line KG-1 where TGF-β1 in combination with TNF-α resulted in an additive suppression while inhibition by TGF-β1 and IFN-α was synergistic. These results demonstrate for the first time the cooperative effects between TGF-β and TNF-α and IFN-α in the suppression of hematopoietic cell growth, raising the possibility that TGF-β might be used in concert with TNF-α or IFN-α in the treatment of various myeloproliferative disorders.