The leukopoietic cytokine granulocyte colony-stimulating factor increases blood flow to rat bone marrow

The current knowledge concerning the blood supply to hematopoietic bone marrow during increased marrow metabolism is scanty. We have previously shown that an accelerated erythropoiesis in the awake rat is accompanied by a rapid increase in perfusion of the tibial marrow and its bony encasement. We have now measured blood flow to tibial marrow and bone in rats with stimulated granulopoiesis, caused by injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF). In awake, adult rats, blood flow was measured with the microsphere method before and at intervals during a 48-hour period after subcutaneous (s.c.) injection of rhG-CSF (10 micrograms/kg). Administration of rhG-CSF caused a marked leukocytosis, mostly due to an increase in blood granulocytes, amounting to 4 times the control value at 8 hours. Concomitantly, the perfusion of tibial marrow rose to about 200% of control by 8 hours before it declined toward baseline. Denervation of the marrow had no effect on this hyperemic response. The perfusion of tibial bone was apparently unaffected by rhG-CSF injection. We conclude that rhG-CSF injection increases blood flow to hematopoietic marrow, but not to bone. This may have important implications for marrow transplantation and drug therapy for patients with marrow failure.