Administration of recombinant human interleukin-7 alters the frequency and number of myeloid progenitor cells in the bone marrow and spleen of mice

The administration of greater than or equal to 5 micrograms interleukin- 7 (IL-7) twice a day to mice for 4 to 7 days increased by twofold to fivefold the total number of splenic and peripheral blood leukocytes, but did not appreciably increase bone marrow (BM) cellularity. This regimen of IL-7 administration also resulted in a greater than 90% reduction in the frequency and total number of single lineage colony- forming unit-culture (CFU-c) and multilineage CFU-granulocyte, erythroid, monocyte, megakaryocyte colonies that could be cultured from the BM, but a fivefold to 15-fold increase in the number of these progenitors that could be cultured from the spleen. All of these effects were reversible with progenitor and white blood cell numbers returning to near normal by day 6. Morphologic analysis of cells obtained from the BM of IL-7-treated mice showed an increase in lymphoid cells. Surface phenotype analysis showed that most of this IL- 7-induced increase in lymphocytes was attributable to an increase in immature B cells (B220+, sIg-), while cells expressing the myelomonocytic markers 8C5 and MAC-1 decreased by twofold to threefold. Further studies showed that the administration of IL-7 to mice that had been rendered leukopenic by the injection of cyclophosphamide (Cy) or 5- fluorouracil (5FU) exhibited a more rapid recovery and/or overshoot in their peripheral blood lymphocytes when compared with mice treated with Cy or 5FU alone. These results show that IL-7 can differentially regulate myelopoiesis in the BM and spleen, while stimulating lymphopoiesis.