Improved recovery of myelosuppression following chemotherapy in mice by combined administration of PSK and various cytokines.
Granulocyte-colony-stimulating factor (G-CSF), granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) were used in combination with PSK, a protein-bound polysaccharide extracted from mycelium of Coriolus versicolor (strain CM101), in myelosuppressed mice. The myelosuppression model consisted of BDF1 mice who received 150 mg/kg 5-fluorouracil (5-FU) intravenously. The peripheral blood leukocyte count during the recovery stage was significantly increased when these cytokines were administered with PSK compared to when the cytokines were used individually. In vitro colony assay revealed that the combination of PSK and any of GM-CSF, IL-3 or stem cell factor (SCF) showed a greater increase in colony numbers than when these materials were administered individually, although G-CSF did not show a synergistic effect with PSK. When bone marrow cells were obtained from mice which had been given PSK or IL-3, the colony assays were made in the presence of PSK or IL-3 in vitro. The greatest increase in the numbers was observed in colonies of the cultured group in the presence of IL-3 after the PSK priming. However, the colony formation potential of PSK was not inhibited by addition of anti-SCF antibody. The above results indicate that the combined administration of PSK with G-CSF, GM-CSF or IL-3 increased the hematological recovery of myelosuppressed mice. Moreover, the phase at which PSK has effects on hematopoietic cells seems to be at a more immature level than with IL-3. The combined administration of PSK and the above cytokines may improve myelosuppression after chemotherapy in patients with malignancy.
Kohgo
Y
Y
Third Department of Internal Medicine, Asahikawa Medical College, Japan.
Hirayama
Y
Y
Sakamaki
S
S
Matsunaga
T
T
Ohi
S
S
Kuga
T
T
Kato
J
J
Niitsu
Y
Y
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007155:Immunologic Factors / Q000008:administration & dosage*; D007377:Interleukin-3 / Q000008:administration & dosage*; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D011509:Proteoglycans / Q000008:administration & dosage*; D013997:Time Factors
D007155:Immunologic Factors; D007377:Interleukin-3; D011509:Proteoglycans; D016179:Granulocyte Colony-Stimulating Factor; C010770:polysaccharide-K; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005472:Fluorouracil