Ultrafiltered pig leukocyte extract (UPLE, IMUNOR) potentiates hematopoiesis-stimulating effects of G-CSF in vitro and improves the outcome of treatment of hematopoietic radiation damage in mice with G-CSF.

Ultrafiltered pig leukocyte extract (UPLE, Imunor), a heterogeneous mixture of low molecular weight (<10 kD) substances released from disintegrated pig leukocytes was tested from the point of view of its hematopoiesis-modulating activities using experiments in vitro and in vivo. Attention was focused especially on evaluation of the contingent ability of UPLE to potentiate the hematopoiesis-stimulating effects of recobinant human granulocyte colony-stimulating factor (G-CSF). Experiments in vitro revealed the capability of sera from mice administered UPLE perorally (p.o.) to stimulate proliferation of progenitor cells for granulocytes and macrophages (GM-CFC) in cultures of normal bone marrow cells. In addition, UPLE, as well as sera from mice given UPLE, added to the cultures in combination with G-CSF enhanced the numbers of GM-CFC significantly over those induced by sera after administration of either of the preparations alone. In in vivo experiments, UPLE was found to increase the counts of GM-CFC per femur and femoral bone marrow cellularity in sublethally irradiated mice when administered p.o. after irradiation in combination with G-CSF in comparison with the effects of G-CSF alone. These results indicate the possibility of using UPLE, a commercially available preparation, for treatment of hematopoietic suppression of various etiology.

Hemopoiesis-stimulating effects and enhanced survival of irradiated mice after peroral or intraperitoneal administration of ultrafiltered pig leukocyte extract (UPLE, IMUNOR).

Ultrafiltered pig leukocyte extract (UPLE, IMUNOR, ImunomedicA, Ustí nad Labem, Czech Republic) administered perorally (p.o.) or intraperitoneally (i.p.) enhanced recovery of the pool of granulocyte-macrophage hemopoietic progenitor cells (GM-CFC) in the bone marrow of normal or sublethally irradiated mice and increased survival of mice exposed to a lethal radiation dose. In experiments in vitro, sera of mice treated with UPLE p.o. or i.p. induced GM-CFC colony formation in cultures of normal mouse bone marrow cells, i.e., produced colony-stimulating activity (CSA). UPLE alone did not induce GM-CFC colony growth, i.e., had no CSA. When UPLE alone or sera of mice administered UPLE p.o. or i.p. were added to bone marrow cultures containing suboptimal concentration of recombinant mouse interleukin-3 (rmIL-3), both UPLE and the sera increased the counts of GM-CFC colonies in comparison with cultures containing only rmIL-3, i.e., produced co-stimulating activity (CoSA). Based on the findings obtained in vitro, it can be hypothesized that the described CSA and CoSA of UPLE may play a role also under in vivo conditions; enhancement of the recovery of hemopoiesis suppressed by ionizing radiation may be due to co-operation of the stimulatory effects of UPLE with the action of cytokines endogenously produced in irradiated tissues.

Positive effects of dialyzable leukocyte extract (DLE) on recovery of mouse haemopoiesis suppressed by ionizing radiation and on proliferation of haemopoietic progenitor cells in vitro.

Dialyzed leukocyte extract (DLE) (Immodin SEVAC, Czech Republic) was shown to enhance the recovery of the pools of hemopoietic stem cells (CFUs) and of granulocyte-macrophage hemopoietic progenitor cells (GM-CFC) in the bone marrow in vivo, as well as to increase the numbers of leukocytes and thrombocytes in the peripheral blood of mice exposed to a sublethal dose of gamma-rays, with an ensuing increase in the numbers of mice surviving the lethal radiation dose. In experiments performed in vitro, DLE or sera of mice administered with DLE were added to cultures of intact mouse bone marrow cells containing suboptimal concentrations of hemopoietic stimulatory cytokines, namely recombinant mouse interleukin-3 (rmIL-3) or recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF); under these experimental conditions, both DLE and sera of mice administered DLE were found to increase the counts of GM-CFC colonies in the cultures. It can be hypothesized on the basis of the findings obtained in vitro that the described co-stimulating activity (CoSA) of DLE may play a role also under in vivo conditions; the enhancement of the recovery of hemopoiesis suppressed by ionizing radiation may be due to a co-operation of the stimulatory effects of DLE with the action of cytokines endogenously produced in irradiated tissues.

Stimulation of hemopoietic colony formation from mouse marrow cells in vitro using human dialyzable leukocyte extracts-IMMODIN-SEVAC.

The influence of dialyzable extract from human leukocytes (DLE) on the in vitro growth of the granulocyte-macrophage colony-forming cell (GM-CFC) colonies from progenitors of mouse bone marrow cells was studied. DLE alone did not induce the colony growth but it modulated the number of colonies if administered together with a colony-stimulating factor (CSF). The costimulatory effect prevailed in a broad range of DLE dilution and the index of increase was enhanced with the lowering of the CSF concentration. The costimulatory augmentation of clonal proliferation of GM-CFC with DLE was further strengthened by addition of indomethacin, thus indicating an intervening role of prostaglandins in the modulatory influence of DLE.