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.