Regulation of hemopoiesis in myelosuppressed mice by human recombinant IL-1 alpha.
Human rIL-1 alpha was shown to be a potent stimulus of granulopoiesis in mice that have been myelosuppressed with cyclophosphamide. Stimulation of granulopoiesis was demonstrated in IL-1-treated mice by an accelerated recovery of granulocyte-macrophage colony-forming cells, bone marrow and splenic granulocytic hyperplasia, and a profound granulocytosis. Granulopoiesis was stimulated by IL-1 in a dose-dependent manner at doses ranging from 0.5 to 50 micrograms/kg. Maximal increases in granulocytes were observed after 4 days of IL-1 treatment. Mice treated with IL-1 also exhibited increased splenic megakaryopoiesis with a resultant increase in the number of peripheral blood platelets. In contrast to these positive effects on hemopoiesis, bone marrow, but not splenic, erythropoiesis was depressed in IL-1-treated mice. IL-1 effects were observed in mice treated with a wide dose range (50 to 300 mg/kg) of cyclophosphamide, with optimal effects occurring at a dose of 200 mg/kg. The doses of IL-1 leading to enhanced granulopoiesis caused only minor and transient changes in selected clinical chemistry parameters and caused no toxicities that were evident by histologic examination of tissues. The stimulation of granulopoiesis in the absence of overt toxicity suggests that IL-1 may be useful clinically to enhance the recovery of granulocytes in myelosuppressed patients.
Benjamin
W R
WR
Roche Research Center, Hoffmann-LaRoche Inc., Nutley, NJ 07110.
Tare
N S
NS
Hayes
T J
TJ
Becker
J M
JM
Anderson
T D
TD
D000818:Animals; D001774:Blood Chemical Analysis; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D003115:Colony-Stimulating Factors; D003520:Cyclophosphamide / Q000008:administration & dosage; D004306:Dose-Response Relationship, Immunologic; D004906:Erythrocyte Count / Q000187:drug effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006098:Granulocytes / Q000187:drug effects; D006133:Growth Substances; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007375:Interleukin-1 / Q000008:administration & dosage*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage*; D013154:Spleen; D013950:Thymus Gland / Q000473:pathology; D013997:Time Factors
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide