The effect of a selective estrogen receptor modulator on the progression of spontaneous autoimmune disease in MRL lpr/lpr mice

L. D. Apelgren, D. L. Bailey, R. L. Fouts, L. Short, N. Bryan, G. F. Evans, George Sandusky, S. H. Zuckerman, A. Glasebrook, T. F. Bumol

Research output: Contribution to journalArticle

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Abstract

The MRL lpr/lpr mouse strain is an animal model for the autoimmune disorder systemic lupus erythematosus (SLE). Pathologic changes in the mice include a severe proliferative glomerulonephritis, lymph node and spleen enlargement, increase in autoantibody titers, and shortened life spans. In the present investigation, female MRL lpr/lpr mice have been dosed po daily for 7 months with the selective estrogen receptor modulator (SERM) LY139478 (4 mg/kg) or 17α-ethinylestradiol (EE2, 1 mg/kg) and compared to vehicle control animals. The LY139478 group had an increase in survival (73% survival at 7 months, P = 0.02) but the EE2-treated animals did not (53% survival at 7 months, P = 0.4) when compared to the control group (32% survival at 7 months). Although there were no reductions in autoantibody levels as determined by anti-DNA antibody ELISA, histological analysis of kidney tissue indicated that both LY139478 and EE2 mitigated the progression of glomerular nephritis which was evident in the controls. In contrast, there were no significant differences in lymph node size although the LY139478 and EE2 groups retained a well-defined sinusoidal region. Finally, flow cytometric analysis documented that thymuses from animals treated for 7 months with LY139478 but not with EE2 contained predominantly CD4+/CD+ T cells consistent with a normal thymic phenotype observed in non-MRL lpr/lpr mouse strains. These studies demonstrate that SERMs may be potentially useful for the treatment of autoimmune disorders.

Original languageEnglish (US)
Pages (from-to)55-63
Number of pages9
JournalCellular Immunology
Volume173
Issue number1
DOIs
StatePublished - Oct 10 1996
Externally publishedYes

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LY 117018
Selective Estrogen Receptor Modulators
Autoimmune Diseases
Autoantibodies
Lymph Nodes
Ethinyl Estradiol
Nephritis
Antinuclear Antibodies
Glomerulonephritis
Systemic Lupus Erythematosus
Thymus Gland
Spleen
Animal Models
Enzyme-Linked Immunosorbent Assay
T-Lymphocytes
Phenotype
Kidney
Control Groups

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Apelgren, L. D., Bailey, D. L., Fouts, R. L., Short, L., Bryan, N., Evans, G. F., ... Bumol, T. F. (1996). The effect of a selective estrogen receptor modulator on the progression of spontaneous autoimmune disease in MRL lpr/lpr mice. Cellular Immunology, 173(1), 55-63. https://doi.org/10.1006/cimm.1996.0251

The effect of a selective estrogen receptor modulator on the progression of spontaneous autoimmune disease in MRL lpr/lpr mice. / Apelgren, L. D.; Bailey, D. L.; Fouts, R. L.; Short, L.; Bryan, N.; Evans, G. F.; Sandusky, George; Zuckerman, S. H.; Glasebrook, A.; Bumol, T. F.

In: Cellular Immunology, Vol. 173, No. 1, 10.10.1996, p. 55-63.

Research output: Contribution to journalArticle

Apelgren, LD, Bailey, DL, Fouts, RL, Short, L, Bryan, N, Evans, GF, Sandusky, G, Zuckerman, SH, Glasebrook, A & Bumol, TF 1996, 'The effect of a selective estrogen receptor modulator on the progression of spontaneous autoimmune disease in MRL lpr/lpr mice', Cellular Immunology, vol. 173, no. 1, pp. 55-63. https://doi.org/10.1006/cimm.1996.0251
Apelgren, L. D. ; Bailey, D. L. ; Fouts, R. L. ; Short, L. ; Bryan, N. ; Evans, G. F. ; Sandusky, George ; Zuckerman, S. H. ; Glasebrook, A. ; Bumol, T. F. / The effect of a selective estrogen receptor modulator on the progression of spontaneous autoimmune disease in MRL lpr/lpr mice. In: Cellular Immunology. 1996 ; Vol. 173, No. 1. pp. 55-63.
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