ANEMIA INDUCED IN SPLENECTOMIZED MICE BY ADMINISTRATION OF RHG-CSF

Normal and splenectomized mice (SPLXM) were given rhG-CSF for 10 to 12 8 days and serial observations were made on blood counts for 128 days. After 10 days, mice were killed for histologic studies. All treatment schedules produced, in addition to elevated white blood counts, a mac rocytic anemia which only partially responded to large doses of Epo. S topping rhG-CSF treatment for 2 days resulted in the return of granulo cytes, lymphocytes, monocytes, platelets and polychromatophilic erythr ocytes to near normal levels, indicating a need for the continued pres ence of rhG-CSF to maintain peripheral blood increases. Treatment of n ormal and SPLXM with rhG-CSF induced marked granulocytic hyperplasia o f the bone marrow with expansion of the granulocytic marrow into the a djoining muscle as in acute myelocytic leukemia. The hyperplasia is gr eater in the SPLXM than in the normal mouse where splenic hyperplasia occurs in all cell lines. The rhG-CSF also results in expansion of gra nulopoiesis into the normally fatty tail bone marrow in SPLXM. The rhG -CSF treatment produced marked increases in the assayable numbers of G M-CFU, G-CFU and M-CFU. The significance and mechanisms of induction o f these changes are not clear. It is speculated that treatment with rh G-CSF has multicellular effects, suggesting that it initiates a cascad e of molecular reactions that cause the effects observed.