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Title: Administration of an immunomodulatory azaspirane, SK F 105685, or human recombinant interleukin 1 stimulates myelopoiesis and enhances survival from lethal irradiation in C57Bl/6 mice

The immunomodulatory azaspirane SK F 105685 has immunosuppressive activity in animal models of autoimmune disease such as adjuvant-induced arthritis and experimental autoimmune encephalomyelitis. The mechanism of SK F 105685 appears to be the induction of nonspecific suppressor cell (SC) activity. SC appear to be null cells, that is, cells that lack specific cell surface markers of mature B cells, T cells, natural killer (NK) cells, or macrophages. Because the authors hypothesized that the induction of SC was associated with enhanced hematopoiesis, they sought to determine the hematopoietic potential of SK F 105685. Recombinant interleukin 1 alpha (rIL-1) was included as a positive control for hematopoietic stimulation in their studies. They demonstrate here that administration of SK F 105685 increases the number of granulocyte-macrophage colony-forming units (CFU-GM) within the bone marrow 24 h after injection in a dose-dependent manner. In addition, the percentage of CFU-GM in S-phase of the cell cycle was significantly increased, as was colony-stimulating activity (CSA) present in the serum of treated animals. In their experiments IL-1 did not increase marrow CFU-GM; however, splenic CFU-GM, the proportion of CFU-GM in S-phase of the cell cycle, and serum CSA were all increased 24 h after a single treatment. Administrationmore » of SK F 105685 24 h prior to lethal irradiation resulted in a dose-related increase in the number of surviving mice. These results demonstrate that SK F 105685 and rIL-1 stimulate myelopoiesis in vivo and suggest a mechanism by which prophylactic treatment with these agents protects mice from otherwise lethal irradiation.« less
Authors:
;  [1]
  1. (Department of Anti-Infectives, Smith Kline Beecham Pharmaceuticals, King of Prussia, PA (United States))
Publication Date:
OSTI Identifier:
5018168
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Hematology (Lawrence, Kansas); (United States); Journal Volume: 19:7
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; IMMUNOSUPPRESSIVE DRUGS; RADIOSENSITIVITY EFFECTS; LYMPHOKINES; BONE MARROW; CELL CYCLE; COLONY FORMATION; DOSE-RESPONSE RELATIONSHIPS; GAMMA RADIATION; HEMATOPOIETIC SYSTEM; LETHAL IRRADIATION; LYMPHOCYTES; MACROPHAGES; MICE; SPLEEN; SURVIVAL CURVES; ANIMAL CELLS; ANIMAL TISSUES; ANIMALS; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY; BODY FLUIDS; CONNECTIVE TISSUE CELLS; DRUGS; ELECTROMAGNETIC RADIATION; GROWTH FACTORS; IONIZING RADIATIONS; IRRADIATION; LEUKOCYTES; MAMMALS; MATERIALS; MITOGENS; ORGANIC COMPOUNDS; ORGANS; PHAGOCYTES; PROTEINS; RADIATIONS; RODENTS; SOMATIC CELLS; TISSUES; VERTEBRATES 560152* -- Radiation Effects on Animals-- Animals