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We compared the erythropoiesis-stimulating effects of ultralow doses of erythropoietin receptors and antibodies to erythropoietin in intact mice. Antibodies to erythropoietin, but not erythropoietin receptors, possessed considerable erythropoiesis-activating properties.

The myelotoxicity and the hemopoiesis recovery effect of etoposide, an antitumor preparation of the podophyllotoxin group, were experimentally studied on mice. It was found that the main role in the hemopoiesis recovery after etoposide administration is related to accelerated proliferation and increased differentiation of the hemopoietic precursor cells.

We compared hemopoiesis-stimulating activities of dry pantohematogen and recombinant granulocyte colony-stimulating factor under conditions of cyclophosphamide-induced myelosuppression. These preparations stimulated regeneration of bone marrow granulomonocytopoiesis by various mechanisms.

Pantohematogen stimulates hemopoiesis in mice with cyclophosphane induced bone marrow hypoplasia. The hemopoiesis recovery activated by pantohematogen is manifested by the granulocyte lineage hyperplasia in the bone marrow, rapid restoration of the polymorphonuclear leukocyte and monocyte counts in the peripheral blood, and the development of neutrophilia and monocytosis. The activation effect of pantohematogen on the bone marrow hemopoiesis is related to stimulating the precursor cell proliferation and differentiation and to increasing the functional activity of the hemopoietic microenvironment.

Specific biological activity of the domestic preparation of recombinant human erythropoietin (RHEPO) in an original pill form was experimentally studied in vitro and in vivo. Administration of the RHEPO parent substance at a concentration of 0.5 10 U/ml significantly accelerated the growth of erythroid colony-forming cells (CFU-E) in the culture of intact nonadherent myelokaryocytes. The erythropoiesis-stimulating properties of the new RHEPO preparation are comparable with those of the well-known injection preparations. The drug action is related to increasing the erythroid cell content in the bone marrow and the reticulocyte and erythrocyte counts in the peripheral blood.

The hemostimulating activity of the drug glycyrram and the recombinant granulocytic-macrophagic colony-stimulating factor (CSF) was compared on models of myelosuppression induced by injection of an alkylating agent cyclophospane (CF) or the antimetabolite 5-fluorouracil (5-FU). It was found that glycerram stimulated hematopoiesis more effectively after 5-FU injection but to a lesser extent (in relation to CSF) in CF injection.

Whether cytostatic-induced disorders of the blood system can be corrected with D-glucuronic acid has been studied in murine experiments. D-glucuronic acid has been demonstrated to selectively stimulate the processes of bone marrow granulomonocytopoiesis both in intact animals and in rats with bone marrow hypoplasia induced by cyclophosphanum. During D-glucuronic acid administration, stimulation of hemopoietic regenerative processes is followed by the development of granulocyte lineage hyperplasia in bone marrow, the rapid restoration of blood polymorphonuclear leukocyte and monocyte counts and the development of neutrophilia and monocytosis.

The mechanisms of regulating influence of D-glucuronic acid on granulomonocytopoiesis++ have been studied by using the model of cyclophosphamide-induced myelodepression. Increase of colony-stimulating and interleukin-1 activities production by hemopoiesis inducing microenvironment cells, the stimulation of hemopoietic islets and the different granulomonocytopoiesis precursor cells forming have been shown to be the base of activating action of D-glucuronic acid on bone marrow granulomonocytopoiesis recovery.

Acute infectious peritonitis simulated in mice was used to show that previous osmotic deterioration of the abdominal mast cell population significantly influenced the function of hemopoiesis-inducing microenvironment (HIM). The earlier production of the colony-stimulating and erythropoietic activities by the non-adhesive myelokaryocytes and the decreased production of these activities by the adhesive cells have been established. The results obtained evidence that mast cells modulate HIM mediating their influence on hemopoiesis under natural conditions of inflammation.

On the model of the acute infectious peritonitis in mice it is shown that the previously osmotic disruption of the peritoneal mast cell population remarkably affects the inflammatory focus, blood and bone-marrow leukocytic reactions. The initial neutrophil accumulation increase and the earlier and more intensive leukocytosis and activation of granulo-monocytopoiesis are established. At the same time the kinetics of monocytes in inflammatory focus is expressed weaker and testifies to the prolongation of the inflammatory response. Thus, in the natural inflammatory conditions mast cells of the inflammatory focus directly or indirectly modulate leukocytes and hematopoiesis.

A model of acute infectious peritonitis in mice demonstrated that the inflammation is attended by marked biphasic activation of bone-marrow granulomonocytopoiesis and that the activation is due in many respects to increased functional activity of elements forming the hemopoiesis-inducing microenvironment. This was suggested by increased colony-stimulating activity of the marrow mononuclear cells and the content of hemopoietic islets in the marrow. The colony-stimulating activity of peripheral blood also increased. It was established that inflammation is also characterized by activation of bone-marrow erythropoiesis, which is linked with increased erythropoietic activity of the hemopoiesis-inducing microenvironment and blood. There was a relation between the hemopoietic changes and the kinetics of leukocytes in the focus of inflammation.

The influence of enkephalins on the medullary hemopoiesis has been studied during stress reaction in noninbred mice. It was shown that leu-enkephalin administration suppressed, while met-enkephalin injection stimulated granulocyto- and erythropoiesis during immobilization stress.

The role of thymus in the regulation of erythropoiesis during stress has been studied in experiments on immobilized mice. The development of pronounced leukopenia due to stimulation of erythro- and granulocytopoiesis was demonstrated. Thymectomy, performed a month before immobilization, abolished the phenomenon of erythropoietic cellularity, indicating an important role of thymus in the regulation of myelopoiesis during stress.