Attenuation of nephritis in lupus-prone mice by thalidomide

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. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.