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 mi ce. The myelosuppression model consisted of BDF1 mice who received 150 mg/kg 5-fluorouracil (5-FU) intravenously. The peripheral blood leuko cyte count during the recovery stage was significantly increased when these cytokines were administered with PSK compared to when the cytoki nes were used individually. In vitro colony assay revealed that the co mbination of PSK and any of GM-CSF, IL-3 or stem cell factor (SCF) sho wed a greater increase in colony numbers than when these materials wer e 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 presen ce of PSK or IL-3 in vitro. The greatest increase in the numbers was o bserved in colonies of the cultured group in the presence of IL-3 afte r the PSK priming. However, the colony formation potential of PSK was not inhibited by addition of anti-SCF antibody. The above results indi cate that the combined administration of PSK with G-CSF, GM-CSF or IL- 3 increased the hematological recovery of myelosuppressed mice. Moreov er, the phase at which PSK has effects on hematopoietic cells seems to be at a more immature level than with IL-3. The combined administrati on of PSK and the above cytokines may improve myelosuppression after c hemotherapy in patients with malignancy.