Recombinant human interleukin-11 treatment enhances collateral vessel growth after femoral artery ligation.
OBJECTIVE
To investigate the role of recombinant human interleukin-11 (rhIL-11) on in vivo mobilization of CD34(+)/vascular endothelial growth factor receptor (VEGFR) 2(+) mononuclear cells and collateral vessel remodeling in a mouse model of hindlimb ischemia.


RESULTS
We observed that treatment of Sv129 mice with continuous infusion of 200-μg/kg rhIL-11 per day led to in vivo mobilization of CD34(+)/VEGFR2(+) cells that peaked at 72 hours. Sv129 mice pretreated with rhIL-11 for 72 hours before femoral artery ligation showed a 3-fold increase in plantar vessel perfusion, leading to faster blood flow recovery; and a 20-fold increase in circulating CD34(+)/VEGFR2(+) cells after 8 days of rhIL-11 treatment. Histologically, experimental mice had a 3-fold increase in collateral vessel luminal diameter after 21 days of rhIL-11 treatment and a 4.4-fold influx of perivascular CD34(+)/VEGFR2(+) cells after 8 days of therapy. Functionally, rhIL-11-treated mice showed better hindlimb appearance and use scores when compared with syngeneic mice treated with PBS under the same experimental conditions.


CONCLUSIONS
These novel findings show that rhIL-11 promotes in vivo mobilization of CD34(+)/VEGFR2(+) mononuclear cells, enhances collateral vessel growth, and increases recovery of perfusion after femoral artery ligation. Thus, rhIL-11 has a promising role for development as an adjunctive treatment of patients with peripheral vascular disease.
McAllister Heart Institute, University of North Carolina, 103 Mason Farm Rd., Chapel Hill, NC 27599-7126, USA. jaitseb@med.unc.edu
Julius
J
Aitsebaomo
Siddharth
S
Srivastava
Hua
H
Zhang
Sushmita
S
Jha
Zhongjing
Z
Wang
Stephan
S
Winnik
Anka N
AN
Veleva
Xinchun
X
Pi
Pamela
P
Lockyer
James E
JE
Faber
Cam
C
Patterson
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*; D006614:Hindlimb / Q000098:blood supply*; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008026:Ligation; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D018952:Antigens, CD34; C508611:IL11 protein, human; D017370:Interleukin-11; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; D040301:Vascular Endothelial Growth Factor Receptor-2