In vivo administration of recombinant interleukin-2 induces granulocyte-macrophage colony formation in a murine system.
The in vivo administration of recombinant interleukin-2 (rIL-2) in humans has led to anemia, thrombocytopenia, and eosinophilia. In an attempt to evaluate the effects of the in vivo administration of rIL-2 on murine bone marrow, we administered rIL-2 to C57BL/6 female mice i.p. three times a day at doses ranging from 10,000 to 100,000 U for 10 days; we then harvested blood and bone marrow from these animals every other day and performed the following analyses: White blood cell count, red blood cell count, hemoglobin concentration, histogram analysis of nucleated cell volume, manual differential counts, and in vitro colony-forming assays for granulocytes and monocytes (CFU-GM). The administration of rIL-2 induced an overall increase in the total white blood cell count that was dose-dependent for its appearance and overall number. This increase was secondary to an increase in monocytes and granulocytes but not to a change in lymphocyte number. Myeloid proliferative activity measured by CFU-GM revealed a biphasic pattern of activity. An early proliferation at 2 days was not followed by lymphocytosis. However, a second peak of proliferation at 6 days was associated with peripheral blood granulocytosis and monocytosis. After rIL-2 was discontinued on day 10, the CFU-GM activity returned to normal by days 16-18. These results suggest that the in vivo administration of rIL-2 may play an important role in the regulation of hematopoiesis.
Division of Surgical Oncology, University of Calgary, Alberta, Canada.
R
R
Lafreniere
B
B
Houwen
C
C
Rankin
K
K
Borkenhagen
M
M
Phillips
D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D005260:Female; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects*; D006410:Hematopoiesis / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D007376:Interleukin-2; D011994:Recombinant Proteins