Interleukin-6 interacts with interleukin-4 and other hematopoietic growth factors to selectively enhance the growth of megakaryocytic, erythroid, myeloid, and multipotential progenitor cells

Abstract

The growth-promoting activities of interleukin-6 (IL-6) in combination with different factors were assessed in bone marrow (BM) cultures prepared from normal mice and from mice treated with 5-fluorouracil (5- FU). Effects on hematopoietic colony formation with respect to number, size, and cellular composition were evaluated. In agreement with previous reports, IL-6 acts synergistically with IL-3 to stimulate increased numbers of granulocyte/macrophage (GM) and multilineage colonies in day-2 and day-4 post-5-FU BM cultures. Furthermore, day 4 but not day 2 post-5-FU BM showed enhanced GM colony formation when stimulated with IL-6 plus interleukin-4 (IL-4) or granulocyte colony- stimulating factor (G-CSF). In contrast, IL-6 did not increase the number of colonies supported by M-CSF or GM-CSF. Nevertheless IL-6 interacted with all factors, including M-CSF and GM-CSF, to stimulate an increase in colony size. Many of these myeloid colonies attained a diameter of greater than or equal to 0.5 mm, suggesting they derive from high proliferative potential cells (HPP-CFC). The response of normal and day-8 post-5-FU BM containing high numbers of more mature progenitors was also assessed. We found IL-6 enhanced colony formation by lineage-restricted megakaryocytic and erythroid progenitors in the presence of IL-3 and IL-4 plus erythropoietin (Epo), respectively. The sum of these results shows that IL-6 interacts with a variety of factors to regulate the growth of progenitor cells at different stages of lineage commitment and maturation.

Production of interleukin‐1β and interleukin‐6 in hepatoblastoma

“…In this respect, hepatoblastoma contrasts with several other malignancies of childhood, which seem to produce TNF-a (Saarinen et al, 1990). So far, no data are available on the occurrence of epidermal growth factor (EGF) or transforming growth factorbeta (TGF-P) in hepatoblastoma, both of which also modulate the effect of IL-6 in acute-phase response (Rokita et al, 1990).…”

Hepatocellular carcinoma producing a granulocyte colony‐stimulating factor: report of a resected case with a literature review

“…The five cases shown in Table 2 were diagnosed as poorly differentiated carcinoma, with the exception of the HCC case 2. G-CSF activity stimulated tumour cell growth in combination with other cytokines, such as IL-6 (9,19). In another study, G-CSF was reported to inhibit tumour necrosis factor a via the effect of IL-1 b…”

Enhanced suppression of human myeloid leukemic cell lines by combinations of IL‐6, LIF, GM‐CSF and G‐CSF

“…Combination of IL-6 with IL-3 accelerated the initiation of murine multilineage colonies in cultures of spleen cells (Ikebuchi et al, 1987). IL-6 synergized with IL-4 or G-CSF to increase the number and size of granulocytes and/or macrophage colonies in murine bone-marrow cultures (Rennick et al, 1989). IL-6 interacted synergistically…”