Attenuation of nephritis in lupus-prone mice by thalidomide
Open Access
- 25 August 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Rheumatology
- Vol. 51 (12), 2131-2140
- https://doi.org/10.1093/rheumatology/kes227
Abstract
Objectives. Thalidomide has various effects, such as immune modulation, anti-angiogenicity, anti-inflammation and anti-proliferation. Moreover, thalidomide modulates the activity of NF-κB, 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 10 mg/kg of thalidomide alone; 1.7, 5 or 10 mg/kg of thalidomide plus 1.5 mg/kg of PL and 33.3 mg/kg of MMF plus PL). Proteinuria and histological damage were evaluated. Immune complex deposition and nuclear translocation of NF-κB 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 10 mg/kg of thalidomide monotherapy showed a significant decrease in proteinuria and significantly lower glomerular and tubular damage scores, comparable to 5 or 10 mg/kg of thalidomide plus PL or MMF plus PL. Also, treatment with 10 mg/kg of thalidomide significantly decreased immune complex accumulation, reduced the serum concentration of anti-dsDNA, IgG2a and IgG2b and inhibited nuclear translocation of NF-κB 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.Keywords
This publication has 37 references indexed in Scilit:
- IFN-α Confers Resistance of Systemic Lupus Erythematosus Nephritis to Therapy in NZB/W F1 MicePublished by The American Association of Immunologists ,2011
- Treatment-related peripheral neuropathy in multiple myeloma: the challenge continuesThe Lancet Oncology, 2010
- Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis TrialAnnals Of The Rheumatic Diseases, 2010
- Overexpression of interleukin-12 and T helper 1 predominance in lupus nephritisClinical and Experimental Immunology, 2008
- Long-term administration of IgG2a anti-NK1.1 monoclonal antibody ameliorates lupus-like disease in NZB/W mice in spite of an early worsening induced by an IgG2a-dependent BAFF/BLyS productionImmunology, 2008
- Pathogenic Role of NF-κB Activation in Tubulointerstitial Inflammatory Lesions in Human Lupus NephritisJournal of Histochemistry & Cytochemistry, 2008
- Thalidomide has both anti-inflammatory and regulatory effects in Behcet's diseaseClinical Rheumatology, 2007
- Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and inductionExpert Opinion on Drug Metabolism & Toxicology, 2006
- Mesangial cell Fas ligand: upregulation in human lupus nephritis and NF-?B-mediated expression in cultured human mesangial cellsClinical and Experimental Nephrology, 2004
- Chronic therapy with recombinant tumor necrosis factor-α in autoimmune NZB/NZW F1 miceClinical Immunology and Immunopathology, 1989