Laquinimod suppression of lupus nephritis in BWF1 mice associates in renal tissue with increase of myeloid suppressor cells and switch of macrophages to anti-inflammatory type II (P5193)

• Published in: The Journal of immunology (1950) Vol. 190; no. 1_Supplement; pp. 68 - 68.24
• Main Authors: Lourenco, Elaine, Wong, Maida, Skaggs, Brian, Matsuura, Isao, Hahn, Bevra
• Format: Journal Article
• Language: English
• Published: 01-05-2013
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.68.24

Abstract
Background: Laquinimod (LAQ) is a novel drug that has been in clinical trial in systemic lupus erythematosus (SLE), an autoimmune disease characterized by nephritis mediated in part by autoantibodies. Aim: We investigated the immunomodulatory properties of LAQ on lupus nephritis in NZB x NZW F1 (BWF1) mice, a murine model for SLE. Methods: Six-month old BWF1 female mice were treated orally 3 times a week with LAQ 25 mg/kg or water. Results: All LAQ-treated animals survived up to 10 weeks after treatment vs 0% survival in controls. No LAQ-treated mouse had proteinuria by week 10 while it was significantly high (3 g/L) in 100% of controls by week 7 after treatment. Examination of kidney specimens showed significantly decreased histologic inflammation, damage, immunoglobulin and C3 deposition in LAQ-treated vs controls. LAQ significantly reduced macrophages (CD11b+) and their expression of MHC, and these cells produced higher levels of IL-10 and lower TNF-alfa vs controls, a phenotype characteristic of anti-inflammatory type II macrophages. In addition, increased frequency of CD11b+Ly6C+Ly6G+ and CD11b+Ly6C+Ly6G- cells was found in LAQ-treated vs controls and these cells suppressed CD4+ T cell proliferation, what characterizes them as myeloid suppressor cells. Conclusion: LAQ suppressed lupus nephritis, improved animals’ survival and increased both anti-inflammatory macrophages and myeloid suppressor cells. Thus, LAQ is a promising therapeutic for human lupus nephritis.