Manipulation of inflammation modulates hyperlipidemia in apolipoprotein E-deficient mice: a possible role for interleukin-6.
There are increasing evidences showing that inflammation participates in atherosclerosis. Therefore, the therapeutic use of anti-inflammatory agents should be considered. We have induced chronic, aseptic inflammation upon the injection of turpentine and tested the effect of dexamethasone on lipoprotein metabolism and, consequently, atherosclerosis in apolipoprotein E-deficient mice. Aseptic inflammation caused a significant decrease in hyperlipidemia. Treatment with dexamethasone elicited the opposite effect increasing hyperlipidemia through mechanisms related to the increase in the synthesis of triglyceride-rich lipoproteins. Changes in plasma lipids correlated with those observed in the size of atherosclerotic lesions. Our data suggest the presence of a common mechanism present in both observations and which is probably related to the cytokine secretion. Among the candidates, we chose to test the effect of interleukin-6 because it is involved in both processes, atherosclerosis and inflammation, and its expression is efficiently repressed by corticosteroids. The injection of recombinant interleukin-6 in our mice elicited the same effects observed in our model of inflammation. We conclude that manipulation of inflammation-related mechanisms modulates lipid homeostasis and development of atherosclerotic plaque in rodents.
Tous
Mònica
M
Centre de Recerca Biomèdica, Institut de Recerca en Ciències de la Salut, IRCIS, Hospital Universitari de Sant Joan, C/Sant Joan s/n, 43201-Reus, Spain.
Ribas
Vicent
V
Escolà-Gil
Joan Carles
JC
Blanco-Vaca
Francisco
F
Calpe-Berdiel
Laura
L
Coll
Blai
B
Ferré
Natàlia
N
Alonso-Villaverde
Carlos
C
Rull
Anna
A
Camps
Jordi
J
Joven
Jorge
J
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000032:analysis; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000139:chemically induced / Q000473:pathology; D001786:Blood Glucose; D001835:Body Weight; D006949:Hyperlipidemias / Q000139:chemically induced / Q000473:pathology*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism*; D008055:Lipids / Q000032:analysis / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014425:Turpentine; D000097202:ATP-Binding Cassette Sub-Family B Member 4
D018435:ATP Binding Cassette Transporter, Subfamily B; D001057:Apolipoproteins E; D001786:Blood Glucose; D015850:Interleukin-6; D008055:Lipids; D014425:Turpentine; D000097202:ATP-Binding Cassette Sub-Family B Member 4