Interleukin-6 interacts with interleukin-4 and other hematopoietic growth
factors to selectively enhance the growth of megakaryocytic, erythroid,
myeloid, and multipotential progenitor cells
D Rennick, J Jackson, G Yang, J Wideman, F Lee and S Hudak
Department of Immunology, DNAX Research Institute, Palo Alto, CA 94304.
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.
Volume 73,
Issue 7,
pp. 1828-1835,
05/15/1989
Copyright © 1989 by The American Society of Hematology
