Effects of late administration of immunoglobulin on experimental atherosclerosis in apolipoprotein E-deficient mice

Circ J. 2005 Dec;69(12):1543-6. doi: 10.1253/circj.69.1543.

Abstract

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.

Methods and 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.

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency*
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / immunology
  • Atherosclerosis / pathology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Count
  • Disease Models, Animal
  • Immunoglobulin Fab Fragments / administration & dosage
  • Immunoglobulin Fab Fragments / pharmacology
  • Immunoglobulins, Intravenous / administration & dosage
  • Immunoglobulins, Intravenous / pharmacology*
  • Immunohistochemistry
  • Macrophages / drug effects
  • Macrophages / pathology
  • Mice
  • Mice, Knockout
  • Treatment Outcome

Substances

  • Apolipoproteins E
  • Immunoglobulin Fab Fragments
  • Immunoglobulins, Intravenous