Effects of late administration of immunoglobulin on experimental atherosclerosis in apolipoprotein E-deficient mice.
BACKGROUND
Although immunoglobulin treatment, beginning simultaneously with the initiation of atherosclerosis, suppresses experimental atherosclerosis in apolipoprotein E-deficient mice, it remains unclear whether the treatment at a subsequent stage of atherosclerosis would be effective.


RESULTS
Experimental atherosclerosis was induced in mice fed a high-fat diet containing 0.3% cholesterol. After confirming the presence of atherosclerotic lesions at 11 weeks, the mice were treated with an intraperitoneal injection of either intact type of immunoglobulin or F(ab')2 fragments of immunoglobulin (both, 1 g.kg-1.day-1) on alternate days over 4 weeks. Fatty streak lesion was suppressed by intact immunoglobulin administration, but not by F(ab')2 fragments of immunoglobulin. Immunohistochemical analysis showed that macrophage and CD4+ T-cell accumulation in the fatty streak lesion was suppressed in mice that received intact immunoglobulin but not in those that received F(ab')2 fragments.


CONCLUSIONS
Immunoglobulin treatment, even at a later stage of atherosclerosis, suppresses the development of lesions associated with the reduced expression of immune-activated cells in fatty streak plaques, demonstrating the benefits of immunoglobulin therapy for prevention of atherosclerosis.
Okabe
Taka-aki
TA
Department of Cadiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan.
Kishimoto
Chiharu
C
Shimada
Kana
K
Murayama
Toshinori
T
Yokode
Masayuki
M
Kita
Toru
T
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D004195:Disease Models, Animal; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D016896:Treatment Outcome
D001057:Apolipoproteins E; D007140:Immunoglobulin Fab Fragments; D016756:Immunoglobulins, Intravenous