PMID- 23674392
OWN - NLM
STAT- MEDLINE
DCOM- 20141208
LR  - 20140324
IS  - 1533-1601 (Electronic)
IS  - 0192-6233 (Linking)
VI  - 42
IP  - 3
DP  - 2014
TI  - Cytokines associated with increased erythropoiesis in Sprague-Dawley rats 
      administered a novel hyperglycosylated analog of recombinant human 
      erythropoietin.
PG  - 540-54
LID - 10.1177/0192623313486318 [doi]
AB  - We previously reported an increased incidence of thrombotic toxicities in 
      Sprague-Dawley rats administered the highest dose level of a hyperglycosylated 
      analog of recombinant human erythropoietin (AMG 114) for 1 month as not solely 
      dependent on high hematocrit (HCT). Thereafter, we identified increased 
      erythropoiesis as a prothrombotic risk factor increased in the AMG 114 high-dose 
      group with thrombotic toxicities, compared to a low-dose group with no toxicities 
      but similar HCT. Here, we identified pleiotropic cytokines as prothrombotic 
      factors associated with AMG 114 dose level. Before a high HCT was achieved, rats 
      in the AMG 114 high, but not the low-dose group, had imbalanced hemostasis 
      (increased von Willebrand factor and prothrombin time, decreased antithrombin 
      III) coexistent with cytokines implicated in thrombosis: monocyte chemotactic 
      protein 1 (MCP-1), MCP-3, tissue inhibitor of metalloproteinases 1, macrophage 
      inhibitory protein-2, oncostatin M, T-cell-specific protein, stem cell factor, 
      vascular endothelial growth factor, and interleukin-11. While no unique pathway 
      to erythropoiesis stimulating agent-related thrombosis was identified, cytokines 
      associated with increased erythropoiesis contributed to a prothrombotic 
      intravascular environment in the AMG 114 high-dose group, but not in lower dose 
      groups with a similar high HCT.
FAU - Andrews, Dina A
AU  - Andrews DA
AD  - 1Comparative Biology Safety Sciences, Pathology, Amgen Inc., Thousand Oaks, 
      California, USA.
FAU - Hamadeh, Hisham K
AU  - Hamadeh HK
FAU - He, Yudong D
AU  - He YD
FAU - Boren, Babette M
AU  - Boren BM
FAU - Turk, James R
AU  - Turk JR
FAU - Boyce, Rogely W
AU  - Boyce RW
FAU - Mytych, Daniel T
AU  - Mytych DT
FAU - Barger, Troy E
AU  - Barger TE
FAU - Salimi-Moosavi, Hossein
AU  - Salimi-Moosavi H
FAU - Sloey, Bethlyn
AU  - Sloey B
FAU - Elliott, Steve
AU  - Elliott S
FAU - McElroy, Patricia
AU  - McElroy P
FAU - Sinclair, Angus M
AU  - Sinclair AM
FAU - Shimamoto, Grant
AU  - Shimamoto G
FAU - Pyrah, Ian T G
AU  - Pyrah IT
FAU - Lightfoot-Dunn, Ruth M
AU  - Lightfoot-Dunn RM
LA  - eng
PT  - Journal Article
DEP - 20130514
PL  - United States
TA  - Toxicol Pathol
JT  - Toxicologic pathology
JID - 7905907
RN  - 0 (Cytokines)
RN  - 0 (Recombinant Proteins)
RN  - 11096-26-7 (Erythropoietin)
SB  - IM
MH  - Animals
MH  - Cytokines/*blood/*metabolism
MH  - Erythropoiesis/*drug effects
MH  - Erythropoietin/chemistry/*pharmacology
MH  - Hematocrit
MH  - Humans
MH  - Male
MH  - Polycythemia
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Proteins/chemistry/*pharmacology
MH  - Reticulocytes
MH  - Thrombosis
OTO - NOTNLM
OT  - coagulation.
OT  - cytokine
OT  - erythropoiesis
OT  - inflammation
OT  - polycythemia
OT  - rat
OT  - thrombosis
EDAT- 2013/05/16 06:00
MHDA- 2014/12/15 06:00
CRDT- 2013/05/16 06:00
PHST- 2013/05/16 06:00 [entrez]
PHST- 2013/05/16 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - 0192623313486318 [pii]
AID - 10.1177/0192623313486318 [doi]
PST - ppublish
SO  - Toxicol Pathol. 2014;42(3):540-54. doi: 10.1177/0192623313486318. Epub 2013 May 
      14.