PMID- 11834721
OWN - NLM
STAT- MEDLINE
DCOM- 20020221
LR  - 20220224
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 90
IP  - 2
DP  - 2002 Feb 8
TI  - Interleukin-18 enhances atherosclerosis in apolipoprotein E(-/-) mice through 
      release of interferon-gamma.
PG  - E34-8
AB  - We have previously shown that interferon-gamma (IFN-gamma) is a potent enhancer 
      of atherogenesis. Interleukin-18 (IL-18) promotes inflammatory responses through 
      release of IFN-gamma, although it can also exert direct actions on other 
      inflammatory mediators. In this present study, we determined the effects of IL-18 
      on atherogenesis and the role of IFN-gamma in this response. Male apolipoprotein 
      E(-/-) mice (apoE(-/-); aged 16 weeks, n=10/group) were fed a normal diet and 
      injected intraperitoneally for 30 days with either recombinant IL-18 (30 
      ng/g/day) or saline. Atherosclerotic lesion size was quantified in 2 vascular 
      beds: the ascending aorta and the aortic arch. IL-18 administration did not 
      affect serum cholesterol concentrations or lipoprotein-cholesterol distribution; 
      however, exogenous IL-18 administration increased lesion size 2-fold in both the 
      ascending aorta (50 642 +/- 12 515 versus 112 399 +/- 13 227 microm(2) P=0.004; 
      saline versus IL-18 groups, respectively) and the aortic arch (3.1 +/- 0.3% 
      versus 6.2 +/- 0.9% area, P=0.006). Exogenous IL-18 promoted a 4-fold increase in 
      the number of lesion-associated T lymphocytes (11 +/- 3 versus 50 +/- 5 cells; 
      P<0.0001) and cells expressing major histocompatability complex class II (9 +/- 3 
      versus 40 +/- 6 cells; P=0.0002). To determine the role of IFN-gamma production 
      in this response, exogenous IL-18 was administered to apoE(-/-) mice that were 
      IFN-gamma deficient. These studies demonstrated that lack of endogenous IFN-gamma 
      ablated the effects of IL-18 on atherosclerosis. Therefore, these data strongly 
      implicates IL-18 in the atherogenic process and suggests that IL-18 increases 
      lesion development through enhancement of an inflammatory response involving an 
      IFN-gamma-dependent mechanism. The full text of this article is available at 
      http://www.circresaha.org.
FAU - Whitman, Stewart C
AU  - Whitman SC
AD  - Gill Heart Institute, Division of Cardiovascular Medicine, University of 
      Kentucky, Lexington, KY 40536-0230, USA.
FAU - Ravisankar, Punnaivanam
AU  - Ravisankar P
FAU - Daugherty, Alan
AU  - Daugherty A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Apolipoproteins E)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Interleukin-18)
RN  - 0 (Lipoproteins)
RN  - 0 (Recombinant Proteins)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Aorta/drug effects/metabolism/pathology
MH  - Aorta, Thoracic/drug effects/metabolism/pathology
MH  - Apolipoproteins E/*deficiency/genetics
MH  - Arteriosclerosis/genetics/pathology/*physiopathology
MH  - Cell Count
MH  - Cholesterol/blood
MH  - Disease Progression
MH  - Drug Administration Schedule
MH  - Histocompatibility Antigens Class II/biosynthesis
MH  - Immunohistochemistry
MH  - Injections, Intraperitoneal
MH  - Interferon-gamma/*biosynthesis/deficiency
MH  - Interleukin-18/administration & dosage/*toxicity
MH  - Lipoproteins/blood
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Recombinant Proteins/administration & dosage/toxicity
MH  - T-Lymphocytes/pathology
EDAT- 2002/02/09 10:00
MHDA- 2002/02/22 10:01
CRDT- 2002/02/09 10:00
PHST- 2002/02/09 10:00 [pubmed]
PHST- 2002/02/22 10:01 [medline]
PHST- 2002/02/09 10:00 [entrez]
AID - 10.1161/hh0202.105292 [doi]
PST - ppublish
SO  - Circ Res. 2002 Feb 8;90(2):E34-8. doi: 10.1161/hh0202.105292.