Glatiramer acetate treatment does not modify the clinical course of (NZB x BXSB)F1 lupus murine model

Int Immunol. 2008 Oct;20(10):1313-9. doi: 10.1093/intimm/dxn086. Epub 2008 Aug 6.

Abstract

Glatiramer acetate (GA, copolymer-1, Copaxone), a therapy approved for treatment of multiple sclerosis (MS), prevents and reverses experimental autoimmune encephalomyelitis, the animal model of MS. In central nervous system autoimmune disease, GA is thought to act through modulation of antigen-presenting cells, such as monocytes, mediating an antigen-independent T(h)2 shift and development of FoxP3+ regulatory T cells. Recent reports indicate that GA may also be effective in models of other autoimmune diseases such as uveoretinitis, inflammatory bowel disease and graft rejection. To date, the potential effect of GA in lupus animal models has not been described. (NZB x BXSB)F1, male mice bearing Y-linked autoimmune acceleration , is a lupus-prone mouse model which is associated with a monocytosis accelerating disease progression. These mice were treated with GA before disease onset until death and both mortality rate and biological parameters were assessed to investigate whether GA may be beneficial in this spontaneous model of systemic lupus erythematosus. GA exerted no beneficial effect on the median survival after up to 7 months of treatment. Humoral and cellular parameters used as markers for lupus progression, such as anti-chromatin, anti-double-stranded DNA and anti-erythrocytes antibodies, hematocrit and monocytosis, were similarly unchanged. Our study demonstrates that GA has no significant effect on the progression of the (NZB x BXSB)F1 lupus-prone animal model. These results reinforce the hypothesis that GA may exert its beneficial effect in some specific autoimmune diseases only.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / blood
  • Chromatin / immunology*
  • Disease Models, Animal
  • Disease Progression
  • Genetic Diseases, Y-Linked / blood
  • Genetic Diseases, Y-Linked / drug therapy
  • Genetic Diseases, Y-Linked / immunology
  • Genetic Diseases, Y-Linked / physiopathology
  • Glatiramer Acetate
  • Hematocrit
  • Immunoglobulins / blood
  • Immunoglobulins / immunology
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / immunology
  • Injections, Subcutaneous
  • Kidney / drug effects
  • Kidney / immunology
  • Kidney / pathology
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / physiopathology
  • Lymphocyte Activation / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NZB
  • Peptides / administration & dosage*
  • Peptides / immunology

Substances

  • Antibodies, Antinuclear
  • Chromatin
  • Immunoglobulins
  • Immunosuppressive Agents
  • Peptides
  • Glatiramer Acetate