In vivo hematopoietic effects of recombinant interleukin-1α in mice: Stimulation of granulocytic, monocytic, megakaryocytic, and early erythroid progenitors, suppression of late-stage erythropoiesis, and reversal of erythroid suppression with erythropoietin

C. S. Johnson, D. J. Keckler, M. I. Topper, P. G. Braunschweiger, Philip Furmanski

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)678-683
Number of pages6
JournalBlood
Volume73
Issue number3
StatePublished - Jan 1 1989
Externally publishedYes

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Erythropoiesis
Erythropoietin
Interleukin-1
Erythroid Precursor Cells
Macrophages
Cytokines
Blood
Bone Marrow
Megakaryocyte Progenitor Cells
Myelopoiesis
Reticulocyte Count
Colony-Stimulating Factors
Granulocyte-Macrophage Progenitor Cells
Injections
Hematopoiesis
Hematopoietic Stem Cells
Intraperitoneal Injections
Hematocrit
Granulocytes
Bone

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

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title = "In vivo hematopoietic effects of recombinant interleukin-1α in mice: Stimulation of granulocytic, monocytic, megakaryocytic, and early erythroid progenitors, suppression of late-stage erythropoiesis, and reversal of erythroid suppression with erythropoietin",
abstract = "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.",
author = "Johnson, {C. S.} and Keckler, {D. J.} and Topper, {M. I.} and Braunschweiger, {P. G.} and Philip Furmanski",
year = "1989",
month = "1",
day = "1",
language = "English (US)",
volume = "73",
pages = "678--683",
journal = "Blood",
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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, Philip

PY - 1989/1/1

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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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