Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:734-742
© 1999 American Heart Association, Inc.
Original Contributions |
The Role of Interleukin 12 in the Development of Atherosclerosis in ApoE-Deficient Mice
From the Division of Cardiovascular Research, Institute of Biomedical Sciences, Academia Sinica (T-S.L., C-C.P., L-Y.C.), and Graduate Institute of Immunology, College of Medicine, National Taiwan University (H-C.Y.), Taipei, Taiwan, R.O.C.
Correspondence to Lee-Young Chau, Division of Cardiovascular Research, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, R.O.C. E-mail lyc{at}mail.ibms.sinica.edu.tw
Abstract—The cytokine
profile of atherosclerotic aortas from apoE-deficient mice was assessed
by reverse transcriptase-polymerase chain reaction. The results clearly
showed that the expression of mRNA for IL-12p40 was evident in aortas
from 3-month-old apoE-deficient mice. The mRNA for IL-10 was detected
in aorta from these mice at the age of 6 months, indicating that
expression of IL-12 is earlier than that of IL-10 in these animals.
Concurrent with IL-12p40, the mRNA for the T-cell cytokine
IFN-
, but not IL-4, was detected in aortas of mice at young and old
ages. Both in situ hybridization and immunostaining
further demonstrated the localization of IL-12 in macrophages
of atherosclerotic lesions. Immunohistochemistry also demonstrated the
expression of costimulatory molecules B7–1 and B7–2 in
macrophages, suggesting that activation of T lymphocytes by
macrophages may occur via surface antigens in lesions. When the
immunoglobulin isotype of the antioxidized LDL antibodies in sera of
apoE-deficient mice was determined, it revealed that both IgM and IgG
were present. Furthermore, IgG2a is predominant and comprises
50% of the antioxidized LDL IgG in sera from young mice (3 months),
but decreased to lower levels (35%) in older mice (6 months). Daily
administration of IL-12 led to an increase in serum levels of
antioxidized LDL antibodies and accelerated
atherosclerosis in young apoE-deficient mice compared
with control mice injected with PBS alone. Taken together, these data
suggest that IL-12 plays an active role in regulating the immune
response during the early phase of atherosclerosis in
apoE-deficient mice.
Key Words: interleukin 12 • atherosclerosis • oxidized LDL
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