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Circulation. 2000;101:908-916

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(Circulation. 2000;101:908.)
© 2000 American Heart Association, Inc.


Basic Science Reports

Interleukin-10 Inhibits Intimal Hyperplasia After Angioplasty or Stent Implantation in Hypercholesterolemic Rabbits

Laurent J. Feldman, MD, PhD; Luc Aguirre, MD; Marianne Ziol, MD, PhD; Jean-Pierre Bridou, BS; Nathalie Nevo, BS; Jean-Baptiste Michel, MD, PhD; P. Gabriel Steg, MD

From U460 INSERM, Faculté Xavier Bichat (L.J.F., L.A., N.N., J.-B.M., P.G.S.); Service de Cardiologie A, Hôpital Bichat (L.J.F., G.S.); Service d’Anatomo-Pathologie, Hôpital Jean Verdier (M.Z.); and Service d’Anatomo-Pathologie, Hôpital Bichat (J.-P.B.); Paris, France.

Correspondence to P. Gabriel Steg, MD, U460 INSERM, Faculté Xavier Bichat, 16, rue Henri Huchard, 75018 Paris, France. E-mail gabriel.steg{at}bch.ap-hop-paris.fr

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.

Methods and 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-1ß 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 {approx}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.


Key Words: interleukins • stents • restenosis




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