Leukocyte-derived interleukin 10 is required for protection against atherosclerosis in low-density lipoprotein receptor knockout mice.
BACKGROUND
Atherosclerosis is an immunoinflammatory disease. Here we examined the role of leukocyte-derived interleukin 10 (IL-10) on advanced atherosclerosis development in low-density lipoprotein receptor knockout (LDLr-/-) mice.


RESULTS
Bone marrow cells harvested from C57BL/6 IL-10-/- and IL-10+/+ mice were transplanted into irradiated male LDLr-/- mice. Four weeks after transplantation, mice were fed a high-fat cholate-free diet for 14 weeks. Despite no differences in weights, serum total, and HDL-cholesterol levels between the 2 groups, IL-10 deficiency in leukocytes induced a >2-fold increase in lesion development in the thoracic aorta compared with controls. We also found a significant 35% increase in aortic root lesion area of IL-10-/- mice compared with IL-10+/+ mice. Furthermore, IL-10 deficiency led to a marked increase in lymphocyte and macrophage accumulation associated with a significant reduction in collagen accumulation. Finally, transfer of IL-10-/- splenocytes to LDLr-/- mice resulted in a 3-fold increase in lesion size in the aortic sinus compared with mice transplanted with IL-10+/+ splenocytes.


CONCLUSIONS
IL-10 expressed by leukocytes prevents exaggerated advanced atherosclerosis development and plays a critical role in modulation of cellular and collagen plaque composition, at least in part, through a modulation of the systemic immune response.
Potteaux
Stéphane
S
Institut National de la Santé et de la Recherche Médicale, U541, Hôpital Lariboisière, Paris, France.
Esposito
Bruno
B
van Oostrom
Olivia
O
Brun
Valérie
V
Ardouin
Patrice
P
Groux
Hervé
H
Tedgui
Alain
A
Mallat
Ziad
Z
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D001025:Aortitis / Q000276:immunology / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016026:Bone Marrow Transplantation; D003094:Collagen / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005355:Fibrosis; D007249:Inflammation; D016753:Interleukin-10 / Q000502:physiology*; D007962:Leukocytes / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D011828:Radiation Chimera; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D013601:T-Lymphocytes / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology
D011973:Receptors, LDL; D016753:Interleukin-10; D003094:Collagen