© 1999 American Heart Association, Inc.
UltraRapid Communication |
Protective Role of Interleukin-10 in Atherosclerosis
From the Institut National de la Santé et de la Recherche Médicale (Z.M., S.B., M.D., B.E., A.T.), INSERM U141 and IFR "Circulation Lariboisière," Paris; Unité Mixte de Recherche (V.D., F.E., M.F.B., F.B., N.D., D.S.), Centre National de la Recherche Scientifique, Rhône Poulenc Rorer, Vitry-sur-Seine; and INSERM U325 (H.D., C.F., B.S.), Département d'Athérosclérose, Institut Pasteur, Lille, France.
Correspondence to Alain Tedgui, INSERM U141, 41, Bd de la Chapelle, 75475 Paris Cedex 10, France. E-mail alain.tedgui{at}inserm.lrb.ap-hop-paris.fr
Abstract—The potential role of
anti-inflammatory cytokines in the modulation of the
atherosclerotic process remains unknown. Interleukin (IL)-10 has potent
deactivating properties in macrophages and T cells and
modulates many cellular processes that may interfere with the
development and stability of the atherosclerotic plaque. IL-10 is
expressed in human atherosclerosis and is associated
with decreased signs of inflammation. In the present study, we show
that IL-10–deficient C57BL/6J mice fed an atherogenic diet and raised
under specific pathogen-free conditions exhibit a significant 3-fold
increase in lipid accumulation compared with wild-type mice.
Interestingly, the susceptibility of IL-10–deficient mice to
atherosclerosis was exceedingly high (30-fold increase)
when the mice were housed under conventional conditions.
Atherosclerotic lesions of IL-10–deficient mice showed increased
T-cell infiltration, abundant interferon-
expression, and decreased
collagen content. In vivo, transfer of murine IL-10 achieved 60%
reduction in lesion size. These results underscore the critical roles
of IL-10 in both atherosclerotic lesion formation and stability.
Moreover, IL-10 appears to be crucial as a protective factor against
the effect of environmental pathogens on
atherosclerosis. The full text of this article is
available at http://www.circresaha.org.
Key Words: interleukin-10 • atherosclerosis • mice • macrophage • lymphocyte • collagen
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