Cross-regulatory roles of interleukin (IL)-12 and IL-10 in atherosclerosis.
T cell cytokines are known to play a major role in determining protection and pathology in infectious disease. It has recently become clear that IL-12 is a key inducer of the type 1 T cell cytokine pattern characterized by production of IFN-gamma. Conversely, IL-10 down-regulates IL-12 production and type 1 cytokine responses. We have investigated whether IL-12 and IL-10 might be involved in a chronic inflammatory reaction, atherosclerosis. In atherosclerotic plaques, we found strong expression of IFN-gamma but not IL-4 mRNAs as compared to normal arteries. IL-12 p40 mRNA and IL-12 p70 protein were also found to be abundant in atherosclerotic plaques. IL-12 was induced in monocytes in vitro in response to highly oxidized LDL but not minimally modified LDL. The cross-regulatory role of IL-10 was indicated by the expression of IL-10 in some atherosclerotic lesions, and the demonstration that exogenous rIL-10 inhibited LDL-induced IL-12 release. These data suggest that the balance between IL-12 and IL-10 production contributes to the level of immune-mediated tissue injury in atherosclerotsis.
Uyemura
K
K
Department of Medicine, University of California, School of Medicine, Los Angeles, USA.
Demer
L L
LL
Castle
S C
SC
Jullien
D
D
Berliner
J A
JA
Gately
M K
MK
Warrier
R R
RR
Pham
N
N
Fogelman
A M
AM
Modlin
R L
RL
D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis*; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis
D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D016753:Interleukin-10; D018664:Interleukin-12