Protective role of interleukin-10 in atherosclerosis.
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-gamma 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.
Mallat
Z
Z
Institut National de la Santé et de la Recherche Médicale, INSERM U141, 75475 Paris Cedex 10, France.
Besnard
S
S
Duriez
M
M
Deleuze
V
V
Emmanuel
F
F
Bureau
M F
MF
Soubrier
F
F
Esposito
B
B
Duez
H
H
Fievet
C
C
Staels
B
B
Duverger
N
N
Scherman
D
D
Tedgui
A
A
D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D005260:Female; D016753:Interleukin-10 / Q000172:deficiency* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL
D016753:Interleukin-10; D002784:Cholesterol