Attenuation of nephritis in lupus-prone mice by thalidomide

Sang Won Lee, Yong Beom Park, Jaeseok Yang, Kyu Hyung Park, Soo Kon Lee, Kyu Hun Choi, Beom Seok Kim

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Abstract

Objectives:Thalidomide has various effects, such as immune modulation, anti-angiogenicity, antiinflammation and anti-proliferation. Moreover, thalidomide modulates the activity of NF-kB, which can up-regulate the expression of downstream genes involved in the pathophysiology of LN. Here we investigated the efficacy of thalidomide monotherapy or thalidomide plus prednisolone (PL) on nephritis in NZB/ WF1 mice at different doses and compared both with a combination therapy of MMF plus PL. Methods: Forty-three female NZB/WF1 mice were divided into eight groups (untreated; 1.7, 5 or 10mg/kg of thalidomide alone; 1.7, 5 or 10mg/kg of thalidomide plus 1.5mg/kg of PL and 33.3mg/kg of MMF plus PL). Proteinuria and histological damage were evaluated. Immune complex deposition and nuclear translocation of NF-kB in kidney tissues were assessed by immunofluorescence staining. Serum concentrations of anti-dsDNA and IgG subclasses were also measured. Results:In comparison with untreated mice, mice treated with 10mg/kg of thalidomide monotherapy showed a significant decrease in proteinuria and significantly lower glomerular and tubular damage scores, comparable to 5 or 10mg/kg of thalidomide plus PL or MMF plus PL. Also, treatment with 10mg/kg of thalidomide significantly decreased immune complex accumulation, reduced the serum concentration of anti-dsDNA, IgG2a and IgG2b and inhibited nuclear translocation of NF-kB in kidney tissues, comparable to standard therapy for LN. Conclusion: These data suggest that thalidomide might play an anti-inflammatory role in the pathophysiology of LN, and it could serve as a complementary therapy to standard induction regimens for refractory LN.

Original languageEnglish
Article numberkes227
Pages (from-to)2131-2140
Number of pages10
JournalRheumatology (United Kingdom)
Volume51
Issue number12
DOIs
Publication statusPublished - 2012 Dec 1

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All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Pharmacology (medical)

Cite this

Lee, S. W., Park, Y. B., Yang, J., Park, K. H., Lee, S. K., Choi, K. H., & Kim, B. S. (2012). Attenuation of nephritis in lupus-prone mice by thalidomide. Rheumatology (United Kingdom), 51(12), 2131-2140. [kes227]. https://doi.org/10.1093/rheumatology/kes227