title: Attenuation of nephritis in lupus-prone mice by thalidomide.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sang-Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Yong-Beom
authors.initials: YB
authors.lastname: Park
authors.forename: Jaeseok
authors.initials: J
authors.lastname: Yang
authors.forename: Kyu-Hyung
authors.initials: KH
authors.lastname: Park
authors.forename: Soo-Kon
authors.initials: SK
authors.lastname: Lee
authors.forename: Kyu Hun
authors.initials: KH
authors.lastname: Choi
authors.forename: Beom Seok
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000936:Antigen-Antibody Complex / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005921:Glomerulonephritis / Q000473:pathology / Q000517:prevention & control; D007074:Immunoglobulin G / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008181:Lupus Nephritis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008814:Mice, Inbred NZB; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology; D011507:Proteinuria / Q000517:prevention & control; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000893:Anti-Inflammatory Agents; D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D013792:Thalidomide; D004247:DNA; D011239:Prednisolone; D009173:Mycophenolic Acid