Interleukin-6 interacts with interleukin-4 and other hematopoietic growth factors to selectively enhance the growth of megakaryocytic, erythroid, myeloid, and multipotential progenitor cells.
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.
Rennick
D
D
Department of Immunology, DNAX Research Institute, Palo Alto, CA 94304.
Jackson
J
J
Yang
G
G
Wideman
J
J
Lee
F
F
Hudak
S
S
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D004338:Drug Combinations; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000378:metabolism* / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4; D015850:Interleukin-6; D007378:Interleukins / Q000378:metabolism* / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor; D008533:Megakaryocytes / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA
D003115:Colony-Stimulating Factors; D004338:Drug Combinations; D006133:Growth Substances; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D015850:Interleukin-6; D007378:Interleukins; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor