Synergistic interactions between interleukin-11 and interleukin-4 in support of proliferation of primitive hematopoietic progenitors of mice.
Interleukin-11 (IL-11) is a newly identified lymphohematopoietic cytokine originally derived from the primate bone marrow stromal cell line, PU-34. Separately, we reported that IL-11 augments IL-3-dependent proliferation of primitive murine hematopoietic progenitors in culture. We have now examined the synergistic interactions between IL-11 and IL-4 in support of colony formation from marrow cells of mice treated 2 days before with 150 mg/kg 5-fluorouracil. Neither recombinant human IL-11 nor murine IL-4 alone was effective in the support of colony formation. When the two factors were combined, there was major enhancement of colony formation, including that of multilineage colony-forming cells. Serial observations (mapping studies) of development of multipotential blast cell colonies indicated that the synergy between IL-11 and IL-4 is due in part to shortening of the dormant period of the stem cells, an effect very similar to that of IL-6 and granulocyte colony-stimulating factor. The combination of IL-11 and IL-4 may be useful in the stimulation of dormant hematopoietic stem cells in vivo.
Musashi
M
M
Department of Medicine, Medical University of South Carolina, Charleston.
Clark
S C
SC
Sudo
T
T
Urdal
D L
DL
Ogawa
M
M
D000818:Animals; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D017370:Interleukin-11; D015847:Interleukin-4 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology*; D051379:Mice
D016207:Cytokines; D017370:Interleukin-11; D007378:Interleukins; D015847:Interleukin-4; D005472:Fluorouracil