Anemia induced in splenectomized mice by administration of rhG-CSF.
Normal and splenectomized mice (SPLXM) were given rhG-CSF for 10 to 128 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 macrocytic anemia which only partially responded to large doses of Epo. Stopping rhG-CSF treatment for 2 days resulted in the return of granulocytes, lymphocytes, monocytes, platelets and polychromatophilic erythrocytes to near normal levels, indicating a need for the continued presence of rhG-CSF to maintain peripheral blood increases. Treatment of normal and SPLXM with rhG-CSF induced marked granulocytic hyperplasia of the bone marrow with expansion of the granulocytic marrow into the adjoining muscle as in acute myelocytic leukemia. The hyperplasia is greater in the SPLXM than in the normal mouse where splenic hyperplasia occurs in all cell lines. The rhG-CSF also results in expansion of granulopoiesis into the normally fatty tail bone marrow in SPLXM. The rhG-CSF treatment produced marked increases in the assayable numbers of GM-CFU, G-CFU and M-CFU. The significance and mechanisms of induction of these changes are not clear. It is speculated that treatment with rhG-CSF has multicellular effects, suggesting that it initiates a cascade of molecular reactions that cause the effects observed.
Cronkite
E P
EP
Medical Department, Brookhaven National Laboratory, Upton, NY 19973.
Burlington
H
H
Shimosaka
A
A
Bullis
J E
JE
Pappas
N
N
D000740:Anemia / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D001772:Blood Cell Count; D001792:Blood Platelets / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004920:Erythropoiesis / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D006098:Granulocytes / Q000473:pathology; D006410:Hematopoiesis / Q000187:drug effects; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009000:Monocytes / Q000473:pathology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D013154:Spleen / Q000473:pathology; D013156:Splenectomy; D013696:Temperature; D013950:Thymus Gland / Q000473:pathology
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor