Interleukin-12 enhances peripheral hematopoiesis in vivo.
Interleukin 12(IL-12) is a cytokine that supports the proliferation and activation of cytotoxic T lymphocytes and natural killer (NK) cells. Recent evidence has suggested that IL-12 also has hematopoietic activities in vitro. We report studies that show that IL-12 has significant in vivo hematopoietic stimulating activity that includes enhancement of peripheral (splenic) hematopoiesis and mobilization of hematopoietic progenitor cells to the peripheral circulation. A single injection of recombinant murine IL-12 significantly reduced the number of bone marrow (BM) colony-forming unit granulocyte-macrophage (CFU-GM) in a time-dependent manner, while concomitantly stimulating high proliferative potential. In contrast, splenic CFU-GM and HPP were increased in a time- and dose-dependent manner. Chronic administration of IL-12 resulted in significant splenic hyperplasia with increased progenitor cells, increased circulating progenitor cells, and BM hypoplasia with decreased progenitor cells. These data show that IL-12 has significant in vivo hematopoietic effects that include the ability to mobilize progenitor cells to the peripheral circulation, which may prove to be of significant benefit for peripheral blood stem cell transplantation. Thus, IL-12 has potential to be an important agent for clinical transplantation because of its hematopoietic mobilization and its previously shown immune augmenting and therapeutic activities. This combination of hematopoietic and immune functions is unique and not achievable with currently used hematopoietic growth factors.
Jackson
J D
JD
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-3135, USA.
Yan
Y
Y
Brunda
M J
MJ
Kelsey
L S
LS
Talmadge
J E
JE
D000818:Animals; D001772:Blood Cell Count; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D005260:Female; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006965:Hyperplasia; D018664:Interleukin-12 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000473:pathology; D013268:Stimulation, Chemical
D011994:Recombinant Proteins; D018664:Interleukin-12