Acute in vivo effects of IL-3 alone and in combination with IL-6 on the blood cells of the circulation and bone marrow.
Recombinant human IL-3 administered intravenously to rats as a single injection induced peripheral neutrophilia and monocytosis beginning at 4 to 6 hours after injection, peaking at 8 hours, and subsiding to normal by 12 to 24 hours. IL-3 did not induce an initial neutropenia such as accompanies endotoxin-, G-CSF-, and TNF-induced neutrophilia, or lymphopenia such as accompanies endotoxin-, IL-1-, and TNF-induced neutrophilia. The IL-3-induced peripheral neutrophilia was accompanied by a decrease in mature marrow neutrophils, indicating that the mechanism of neutrophilia was through marrow release rather than by demargination, which occurs after the administration of epinephrine or IL-6. The release of mature marrow neutrophils further suggests that IL-3 either has intrinsic neutrophil releasing activity or indirectly causes neutrophil release through the gene expression of a second cytokine. IL-3 induced a striking left-shifted myeloid hyperplasia in the bone marrow at 8 hours that morphologically was very similar to that observed after administration of endotoxin, a finding consistent with the hypothesis of previous investigators that endotoxin may in part act indirectly on hematopoietic cells by eliciting local marrow production of IL-3. Finally, IL-3 induced an increase in marrow pronormoblasts at 8 hours, consistent with the in vitro proliferative effect of IL-3 on erythroid stem cells. The combination of IL-3 and IL-6 induced a synergistic peripheral neutrophilia and monocytosis and a striking synergistic increase in marrow mast cells. The combination of IL-3 and IL-6 also induced an erythroid and left-shifted myeloid hyperplasia such as would be expected given the individual effects of these hematopoietic growth factors.
Ulich
T R
TR
Department of Pathology, University of California, College of Medicine, Irvine 92717.
del Castillo
J
J
Busser
K
K
Guo
K Z
KZ
Yin
S M
SM
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects*; D007275:Injections, Intravenous; D007377:Interleukin-3 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew
D007377:Interleukin-3; D015850:Interleukin-6