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Mycophenolate mofetil suppresses autoimmunity and mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus.

Publication ,  Journal Article
McMurray, RW; Elbourne, KB; Lagoo, A; Lal, S
Published in: J Rheumatol
December 1998

OBJECTIVE: To examine the effects of the immunosuppressant, mycophenolate mofetil (MM), on autoimmunity, glomerulonephritis, and mortality in the female NZB x NZW F1 (B/W) mouse model of systemic lupus erythematosus (SLE). METHODS: The development of murine lupus was assessed during the lifespan of 10 female B/W mice given 200 mg/kg/day of MM compared to 10 female B/W mice given vehicle. At 6 week intervals, mice were examined for weight change, albuminuria, antibodies to DNA, and IgG immunoglobulin levels. Morbidity and mortality were assessed daily. In a parallel study, MM treated and control B/W mice were examined at 18 weeks of age for splenocyte phenotype and adhesion molecule expression, as well as antibody titers and in vitro cytokine production in response to immunization with dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH). RESULTS: The administration of MM was well tolerated without apparent side effects. Weight gain in MM treated and control mice was identical through 36 weeks of age. In the treatment group, MM suppressed the development of albuminuria and anti-DNA antibodies compared to the control animals. There were no significant differences between groups in serum concentrations of total IgG. At 60 weeks of age survival in the MM treated group was 100% compared to 10% in the control group. MM did not alter the percentages of CD4, CD8, or IgM positive splenocytes; however, the percentage of CD4+ T lymphocytes expressing very late antigen 4 and intercellular adhesion molecule 1 was reduced. MM inhibited the antibody response to DNP-KLH immunization in vivo; however, in vitro cytokine production in response to KLH was not suppressed. CONCLUSION: MM suppressed the development of autoimmunity and prolonged lifespan in the female B/W mouse model of SLE. Suppression of autoimmunity was achieved without obvious side effects or altered CD4:CD8 T cell ratios. MM may be a useful primary or adjunctive therapy in human SLE.

Duke Scholars

Published In

J Rheumatol

ISSN

0315-162X

Publication Date

December 1998

Volume

25

Issue

12

Start / End Page

2364 / 2370

Location

Canada

Related Subject Headings

  • Treatment Outcome
  • Survival Analysis
  • Spleen
  • Mycophenolic Acid
  • Mice, Inbred Strains
  • Mice, Inbred NZB
  • Mice
  • Lupus Erythematosus, Systemic
  • Kidney Glomerulus
  • Kidney
 

Citation

APA
Chicago
ICMJE
MLA
NLM
McMurray, R. W., Elbourne, K. B., Lagoo, A., & Lal, S. (1998). Mycophenolate mofetil suppresses autoimmunity and mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus. J Rheumatol, 25(12), 2364–2370.
McMurray, R. W., K. B. Elbourne, A. Lagoo, and S. Lal. “Mycophenolate mofetil suppresses autoimmunity and mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus.J Rheumatol 25, no. 12 (December 1998): 2364–70.

Published In

J Rheumatol

ISSN

0315-162X

Publication Date

December 1998

Volume

25

Issue

12

Start / End Page

2364 / 2370

Location

Canada

Related Subject Headings

  • Treatment Outcome
  • Survival Analysis
  • Spleen
  • Mycophenolic Acid
  • Mice, Inbred Strains
  • Mice, Inbred NZB
  • Mice
  • Lupus Erythematosus, Systemic
  • Kidney Glomerulus
  • Kidney