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.

Abstract

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 we hypothesized that the induction of SC was associated with enhanced hematopoiesis, we 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 our studies. We 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 our 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. Administration 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.

• Authors: A G King, A M Badger
• Journal: Experimental hematology (Exp Hematol) Vol. 19 Issue 7 Pg. 624-8 (Aug 1991) ISSN: 0301-472X [Print] Netherlands
• PMID: 1893948 (Publication Type: Journal Article)

Chemical References

• Adjuvants, Immunologic
• Colony-Stimulating Factors
• Interleukin-1
• Recombinant Proteins
• Spiro Compounds
• SK&F 105685

Topics

• Adjuvants, Immunologic (pharmacology)
• Animals
• Bone Marrow (radiation effects)
• Bone Marrow Cells
• Colony-Stimulating Factors (blood)
• Female
• Gamma Rays
• Granulocytes (cytology)
• Hematopoiesis (drug effects, radiation effects)
• Hematopoietic Stem Cells (cytology)
• Interleukin-1 (pharmacology)
• Macrophages (cytology)
• Mice
• Mice, Inbred C57BL
• Recombinant Proteins (pharmacology)
• S Phase (drug effects)
• Spiro Compounds (pharmacology)
• Spleen (cytology)