Effects of interleukin-11 on the hematopoietic action of granulocyte colony-stimulating factor.
Interleukin-11 (IL-11, CAS 145941-26-0) is a cytokine that ameliorates thrombocytopenia induced by chemotherapy. Granulocyte colony-stimulating factor (G-CSF) is frequently used clinically as an adjuvant therapy to ameliorate neutropenia. In this study, it has been investigated whether IL-11 influences the hematopoietic action of G-CSF in vitro. IL-11 alone did not stimulate CFU-Meg colony formation in the absence of interleukin-3 (IL-3), but did in the presence of IL-3. However, IL-11 alone stimulated the formation of CFU-E, BFU-E and CFU-GM colonies, which were further enhanced by IL-3. G-CSF alone stimulated in a concentration dependent manner colony formation of CFU-GM and CFU-E, but not BFU-E or CFU-Meg. The addition of IL-11 enhanced the stimulatory effect of G-CSF on CFU-GM colony formation, and enabled G-CSF to stimulate colony formation of BFU-E, but not CFU-E. The addition of IL-3 further enhanced the stimulatory effect of G-CSF on CFU-E, BFU-E, and CFU-GM colony formation. However, G-CSF was unable to stimulate CFU-Meg colony formation for any of the cytokine combinations tested. These studies demonstrate that IL-11 has significant stimulatory effects on G-CSF-induced CFU-GM colony formation, suggesting that the therapeutic combination of the two growth factors could be beneficial for the treatment of myelosuppression induced by chemotherapy.
Momose
Kazuhiro
K
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Taguchi
Katsunari
K
Saitoh
Minori
M
Yasuda
Shuhei
S
Miyata
Keiji
K
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D015672:Erythroid Precursor Cells / Q000187:drug effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006397:Hematinics / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D017370:Interleukin-11 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology; D013926:Thrombopoietin / Q000187:drug effects
D006397:Hematinics; D017370:Interleukin-11; D007377:Interleukin-3; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D013926:Thrombopoietin