TY - JOUR
T1 - In vivo hematopoietic effects of recombinant interleukin-1α in mice
T2 - Stimulation of granulocytic, monocytic, megakaryocytic, and early erythroid progenitors, suppression of late-stage erythropoiesis, and reversal of erythroid suppression with erythropoietin
AU - Johnson, C. S.
AU - Keckler, D. J.
AU - Topper, M. I.
AU - Braunschweiger, P. G.
AU - Furmanski, P.
PY - 1989
Y1 - 1989
N2 - Interleukin-1α (IL-1α) is a macrophage-derived, multifunctional cytokine that broadly potentiates myelopoiesis and induces the synthesis of hematopoietic colony-stimulating factors (CSF) in vitro and in vivo. To evaluate the possibility for use of IL-1α in ameliorating in vivo bone marrow suppression induced by drugs or radiation, we examined the in vivo effects of the cytokine on erythropoietic and other hematopoietic progenitor cells. Normal mice were treated with a single intraperitoneal (IP) injection of recombinant human IL-1α at varying doses and were assayed at various times post-treatment. By six hours postinjection, a significant suppression of mature erythroid progenitors (CFU-E) was observed in animals treated with IL-1α (0.5 μg/mouse), with maximum suppression of CFU-E and peripheral blood reticulocyte counts occurring at 24 hours. Decreases in peripheral blood hematocrit did not occur after a single IL-1α injection but were observed after multiple injections of the cytokine. The suppressive effects of IL-1α on late-stage erythropoiesis were abrogated by simultaneous administration of erythropoietin (EPO). At 48 hours post-treatment, a marked stimulation was observed in the numbers of spleen and marrow immature erythroid (BFU-E), macrophage (CFU-M), granulocyte (CFU-G), granulocyte-macrophage (CFU-GM), and megakaryocyte (CFU-meg) progenitor cells. These results demonstrate the potential use of IL-1α as a generalized stimulator of hematopoiesis and show that the cytokine-induced suppression of late-stage erythropoiesis can be prevented by EPO.
AB - Interleukin-1α (IL-1α) is a macrophage-derived, multifunctional cytokine that broadly potentiates myelopoiesis and induces the synthesis of hematopoietic colony-stimulating factors (CSF) in vitro and in vivo. To evaluate the possibility for use of IL-1α in ameliorating in vivo bone marrow suppression induced by drugs or radiation, we examined the in vivo effects of the cytokine on erythropoietic and other hematopoietic progenitor cells. Normal mice were treated with a single intraperitoneal (IP) injection of recombinant human IL-1α at varying doses and were assayed at various times post-treatment. By six hours postinjection, a significant suppression of mature erythroid progenitors (CFU-E) was observed in animals treated with IL-1α (0.5 μg/mouse), with maximum suppression of CFU-E and peripheral blood reticulocyte counts occurring at 24 hours. Decreases in peripheral blood hematocrit did not occur after a single IL-1α injection but were observed after multiple injections of the cytokine. The suppressive effects of IL-1α on late-stage erythropoiesis were abrogated by simultaneous administration of erythropoietin (EPO). At 48 hours post-treatment, a marked stimulation was observed in the numbers of spleen and marrow immature erythroid (BFU-E), macrophage (CFU-M), granulocyte (CFU-G), granulocyte-macrophage (CFU-GM), and megakaryocyte (CFU-meg) progenitor cells. These results demonstrate the potential use of IL-1α as a generalized stimulator of hematopoiesis and show that the cytokine-induced suppression of late-stage erythropoiesis can be prevented by EPO.
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U2 - 10.1182/blood.v73.3.678.bloodjournal733678
DO - 10.1182/blood.v73.3.678.bloodjournal733678
M3 - Article
C2 - 2783864
AN - SCOPUS:0024589701
VL - 73
SP - 678
EP - 683
JO - Blood
JF - Blood
SN - 0006-4971
IS - 3
ER -