Lithium stimulation of diffusion chamber colony growth is mediated by factors other than colony-stimulating factor.
Lithium is a recognized, potent stimulator of granulopoiesis. The present study used the model of clonal growth of granulopoietic precursors in diffusion chambers to investigate the relevance of certain colony-stimulating factors to lithium stimulation in vivo. In this system, lithium stimulation of granulopoiesis could not be attributed to changes in serum or chamber fluid colony-stimulating factor levels. Antibody to colony-stimulating factor-1 administered during culture markedly reduced morphologic expression of colonies in control and lithium-pretreated host mice, yet subculture of chamber contents revealed that lithium stimulation of a granulopoietic progenitor, perhaps of primitive potentiality, had nevertheless occurred. Therefore, we hypothesize that lithium acts in an indirect, hormonal fashion and that these colony-stimulating factors, while necessary for morphologic expression, play no role in the stimulatory effect. This hypothesis raises the possibility that lithium in combination with recombinant colony-stimulating factors may result in clinically effective synergistic stimulation of granulopoiesis.
Doukas
M A
MA
Department of Medicine, University of Kentucky, Lexington.
Shadduck
R K
RK
Waheed
A
A
Gass
C
C
D000818:Animals; D001681:Biological Assay; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000032:analysis; D015194:Diffusion Chambers, Culture; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000032:analysis; D006410:Hematopoiesis / Q000187:drug effects*; D008094:Lithium / Q000032:analysis / Q000494:pharmacology*; D016651:Lithium Carbonate; D051379:Mice; D008813:Mice, Inbred ICR; D011863:Radioimmunoassay
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D016651:Lithium Carbonate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008094:Lithium