THE LEUKOPOIETIC CYTOKINE GRANULOCYTE-COLONY-STIMULATING FACTOR INCREASES BLOOD-FLOW TO RAT BONE-MARROW

The current knowledge concerning the blood supply to hematopoietic bon e marrow during increased marrow metabolism is scanty. We have previou sly shown that an accelerated erythropoiesis in the awake rat is accom panied by a rapid increase in perfusion of the tibial marrow and its b ony encasement. We have now measured blood flow to tibial marrow and b one in rats with stimulated granulopoiesis, caused by injection of rec ombinant human granulocyte colony-stimulating factor (rhG-CSF). In awa ke, adult rats, blood flow was measured with the microsphere method be fore and at intervals during a 48-hour period after subcutaneous (s.c. ) injection of rhG-CSF (10 mu g/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, th e perfusion of tibial marrow rose to about 200% of control by 8 hours before it declined toward baseline. Denervation of the marrow had no e ffect on this hyperemic response. The perfusion of tibial bone was app arently unaffected by rhG-CSF injection. We conclude that rhG-CSF inje ction increases blood flow to hematopoietic marrow, but not to bone. T his may have important implications for marrow transplantation and dru g therapy for patients with marrow failure.