Atheroprotective effect of adjuvants in apolipoprotein E knockout mice.
Strategies aimed at treating atherosclerosis by immunization protocols are emerging. Such protocols commonly use adjuvants as non-specific stimulators of immune responses. However, adjuvants are known to modify various disease processes. The aim of this study was to determine whether adjuvants alter the development of atherosclerosis. We performed immunization protocols in apolipoprotein E knockout mice (E degrees ) following chronic administration schedules commonly employed in experimental atherosclerosis. Our results point out a dramatic effect of several adjuvants on the development of atherosclerosis; three of the four adjuvants tested reduced lesion size. The Alum adjuvant, which is the adjuvant currently used in most vaccination protocols in humans, displayed a strong atheroprotective effect. Mechanisms accounting for atheroprotective effect of Freund's adjuvants included their capacity to increase both Th2 responses and anti-MDA-LDL IgM titers, and/or to impose atheroprotective lipoprotein profiles. The present study indicates that adjuvants have potent atheromodulating capabilities, and thus, implies that the choice of adjuvant is crucial in long-term immunization protocols in experimental atherosclerosis.
Khallou-Laschet
J
J
INSERM U681, Institut Biomédical des Cordeliers, 15, rue de l'Ecole de Médecine, Paris, France.
Tupin
E
E
Caligiuri
G
G
Poirier
B
B
Thieblemont
N
N
Gaston
A-T
AT
Vandaele
M
M
Bleton
J
J
Tchapla
A
A
Kaveri
S V
SV
Rudling
M
M
Nicoletti
A
A
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000534:Alum Compounds / Q000627:therapeutic use*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D005620:Freund's Adjuvant / Q000627:therapeutic use*; D008401:Gas Chromatography-Mass Spectrometry; D007114:Immunization / Q000379:methods*; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013997:Time Factors; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000888:Antibodies, Anti-Idiotypic; D001057:Apolipoproteins E; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C041524:aluminum sulfate; D005620:Freund's Adjuvant