Abstract
Tumor necrosis factor-α (TNF) is a monokine produced by activated macrophages that has cytotoxic and cytostatic effects on erythroid progenitor cells. We have recently shown that Chinese hamster ovary cells transfected with the human TNF gene and which constitutively express TNF induced a hypoproliferative anemia, mild thrombocytopenia, and mild leukocytosis when injected into nude mice. We have used this murine model to determine if treatment with recombinant human erythropoietin can prevent or ameliorate the anemia seen with long-term continuous exposure to high concentrations of TNF. Mice bearing TNF-producing tumors became anemic with hematocrits ranging from 30 to 32%. Treatment with recombinant human erythropoietin (100-1000 U/kg body weight three times per week) increased the reticulocyte counts initially in mice bearing TNF-producing tumors but failed to reverse the anemia seen in these animals. Erythropoietin did not significantly increase the number of marrow erythroid colony-forming units (CFU-E) or erythroid burst-forming units (BFU-E) in mice bearing TNF-producing tumors. The data suggest that erythropoietin could not sufficiently overcome the decreased number of erythroid progenitors in mice bearing tumors producing high levels of TNF to correct their anemia.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 438-441 |
| Number of pages | 4 |
| Journal | Experimental Hematology |
| Volume | 18 |
| Issue number | 5 |
| State | Published - 1990 |
| Externally published | Yes |
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Keywords
- Anemia
- Erythroid progenitors
- Erythropoietin
- TNF
ASJC Scopus subject areas
- Cancer Research
- Cell Biology
- Genetics
- Hematology
- Oncology
- Transplantation
Cite this
Erythropoietin fails to reverse the anemia in mice continuously exposed to tumor necrosis factor-alpha in vivo. / Clibon, U.; Bonewald, Lynda; Caro, J.; Roodman, G. David.
In: Experimental Hematology, Vol. 18, No. 5, 1990, p. 438-441.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Erythropoietin fails to reverse the anemia in mice continuously exposed to tumor necrosis factor-alpha in vivo
AU - Clibon, U.
AU - Bonewald, Lynda
AU - Caro, J.
AU - Roodman, G. David
PY - 1990
Y1 - 1990
N2 - Tumor necrosis factor-α (TNF) is a monokine produced by activated macrophages that has cytotoxic and cytostatic effects on erythroid progenitor cells. We have recently shown that Chinese hamster ovary cells transfected with the human TNF gene and which constitutively express TNF induced a hypoproliferative anemia, mild thrombocytopenia, and mild leukocytosis when injected into nude mice. We have used this murine model to determine if treatment with recombinant human erythropoietin can prevent or ameliorate the anemia seen with long-term continuous exposure to high concentrations of TNF. Mice bearing TNF-producing tumors became anemic with hematocrits ranging from 30 to 32%. Treatment with recombinant human erythropoietin (100-1000 U/kg body weight three times per week) increased the reticulocyte counts initially in mice bearing TNF-producing tumors but failed to reverse the anemia seen in these animals. Erythropoietin did not significantly increase the number of marrow erythroid colony-forming units (CFU-E) or erythroid burst-forming units (BFU-E) in mice bearing TNF-producing tumors. The data suggest that erythropoietin could not sufficiently overcome the decreased number of erythroid progenitors in mice bearing tumors producing high levels of TNF to correct their anemia.
AB - Tumor necrosis factor-α (TNF) is a monokine produced by activated macrophages that has cytotoxic and cytostatic effects on erythroid progenitor cells. We have recently shown that Chinese hamster ovary cells transfected with the human TNF gene and which constitutively express TNF induced a hypoproliferative anemia, mild thrombocytopenia, and mild leukocytosis when injected into nude mice. We have used this murine model to determine if treatment with recombinant human erythropoietin can prevent or ameliorate the anemia seen with long-term continuous exposure to high concentrations of TNF. Mice bearing TNF-producing tumors became anemic with hematocrits ranging from 30 to 32%. Treatment with recombinant human erythropoietin (100-1000 U/kg body weight three times per week) increased the reticulocyte counts initially in mice bearing TNF-producing tumors but failed to reverse the anemia seen in these animals. Erythropoietin did not significantly increase the number of marrow erythroid colony-forming units (CFU-E) or erythroid burst-forming units (BFU-E) in mice bearing TNF-producing tumors. The data suggest that erythropoietin could not sufficiently overcome the decreased number of erythroid progenitors in mice bearing tumors producing high levels of TNF to correct their anemia.
KW - Anemia
KW - Erythroid progenitors
KW - Erythropoietin
KW - TNF
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UR - http://www.scopus.com/inward/citedby.url?scp=0025108516&partnerID=8YFLogxK
M3 - Article
C2 - 2338132
AN - SCOPUS:0025108516
VL - 18
SP - 438
EP - 441
JO - Experimental Hematology
JF - Experimental Hematology
SN - 0301-472X
IS - 5
ER -