Interleukin-10 inhibits intimal hyperplasia after angioplasty or stent implantation in hypercholesterolemic rabbits.
BACKGROUND
Intimal hyperplasia after stent implantation is the main cause of in-stent restenosis. Activated monocytes play a key role in intimal growth. The anti-inflammatory cytokine interleukin-10 (IL-10) is a potent monocyte deactivator, endogenously produced in the atherosclerotic plaque. We tested the hypothesis that exogenous IL-10 may limit postangioplasty intimal hyperplasia after balloon angioplasty or stenting.


RESULTS
Hypercholesterolemic rabbits were treated with recombinant human IL-10 (rhuIL-10) for 3 days after balloon angioplasty or 28 days after stent implantation. High IL-10 serum levels and intense deactivation of circulating monocytic cells, assessed by inhibition of IL-1beta release by lipopolysaccharide-stimulated whole blood, were detected for at least 8 hours after rhuIL-10 intravenous injection (ELISA). Morphometric analyses, performed 28 days after injury, indicated that rhuIL-10 reduced intimal growth by approximately 50% after balloon angioplasty or stenting, resulting in more preserved lumen in stented arteries. Moreover, rhuIL-10 reduced macrophage infiltration by 67% and proliferative activity by 81% in the intima and the media. No toxic effect was detected except minor changes in blood cell count.


CONCLUSIONS
The anti-inflammatory cytokine rhuIL-10 reduces postinjury intimal hyperplasia. The potent attenuation of in-stent intimal growth by rhuIL-10 and its favorable toxicity profile suggest that rhuIL-10 may be useful in the prevention of in-stent restenosis.
Feldman
L J
LJ
U460 INSERM, Faculté Xavier Bichat, Paris, France.
Aguirre
L
L
Ziol
M
M
Bridou
J P
JP
Nevo
N
N
Michel
J B
JB
Steg
P G
PG
D000818:Animals; D002404:Catheterization / Q000009:adverse effects*; D003327:Coronary Disease / Q000209:etiology / Q000517:prevention & control* / Q000628:therapy; D003864:Depression, Chemical; D004036:Diet, Atherogenic; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications*; D006965:Hyperplasia; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D007962:Leukocytes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D012008:Recurrence; D013045:Species Specificity; D015607:Stents / Q000009:adverse effects*; D017539:Tunica Intima / Q000293:injuries / Q000473:pathology*; D014657:Vasculitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D016753:Interleukin-10