PMID- 2303102
OWN - NLM
STAT- MEDLINE
DCOM- 19900328
LR  - 20081121
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 18
IP  - 2
DP  - 1990 Feb
TI  - In vivo suppression of erythropoiesis by tumor necrosis factor-alpha (TNF-alpha): 
      reversal with exogenous erythropoietin (EPO).
PG  - 109-13
AB  - Tumor necrosis factor-alpha (TNF-alpha) selectively kills tumor cells in vitro 
      and in vivo and is being tested as a cancer therapeutic agent. We have shown that 
      TNF-alpha significantly suppresses late-stage erythropoiesis, leading to anemia 
      in chronically treated mice. These erythropoietic effects could limit the 
      clinical use of TNF-alpha. Therefore, we have examined whether erythropoietin 
      (EPO) could be used to prevent TNF-alpha-induced erythroid suppression. Normal 
      mice were treated with a single dose of recombinant murine TNF-alpha (10(5) 
      U/mouse, i.p.) with and without various concentrations of recombinant human EPO. 
      After 3 days, effects on late-stage erythropoiesis were measured by determining 
      the number of mature erythroid colony-forming cells (CFU-E) in the spleen and 
      bone marrow. Simultaneous treatment with EPO abrogated the suppressive effect of 
      TNF-alpha in a dose-dependent manner. EPO treatment also prevented the decrease 
      in peripheral blood-hematocrit that was observed with chronic (5 x 10(4) 
      U/mouse/day for 5 days) administration of TNF-alpha. TNF-alpha-induced 
      hemorrhagic necrosis of tumors and stimulation of macrophage (CFU-M) progenitors 
      were unaffected by EPO treatment. These results demonstrate that simultaneous 
      injection of EPO can abrogate the TNF-alpha-induced suppressive effects on 
      erythropoiesis.
FAU - Johnson, C S
AU  - Johnson CS
AD  - Laboratory of Experimental Hematology, AMC Cancer Research Center, Denver, CO 
      80214.
FAU - Cook, C A
AU  - Cook CA
FAU - Furmanski, P
AU  - Furmanski P
LA  - eng
GR  - CA33188/CA/NCI NIH HHS/United States
GR  - CA45674/CA/NCI NIH HHS/United States
GR  - CA48077/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11096-26-7 (Erythropoietin)
SB  - IM
MH  - Anemia/prevention & control
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Erythroid Precursor Cells/drug effects
MH  - Erythropoiesis/*drug effects
MH  - Erythropoietin/pharmacology
MH  - Hematocrit
MH  - Hematopoietic Stem Cells/drug effects
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1990/02/01 00:00
MHDA- 1990/02/01 00:01
CRDT- 1990/02/01 00:00
PHST- 1990/02/01 00:00 [pubmed]
PHST- 1990/02/01 00:01 [medline]
PHST- 1990/02/01 00:00 [entrez]
PST - ppublish
SO  - Exp Hematol. 1990 Feb;18(2):109-13.