Deletion of IL-18 receptor ameliorates renal injury in bovine serum albumin-induced glomerulonephritis

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2008-07, Vol.128 (1), p.103-108
• Main Authors: Sugiyama, Masafumi, Kinoshita, Koji, Kishimoto, Kazuya, Shimazu, Hideki, Nozaki, Yuji, Ikoma, Shinya, Funauchi, Masanori
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Antigen-Antibody Complex; Biological and medical sciences; BSA; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glomerulonephritis; Glomerulonephritis - chemically induced; Glomerulonephritis - metabolism; Glomerulonephritis - pathology; IL-18; Immunohistochemistry; Interferon-gamma - biosynthesis; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Nephritis; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Proteinuria - chemically induced; Receptors, Interleukin-18 - deficiency; Receptors, Interleukin-18 - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Serum Albumin, Bovine - toxicity; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2008.03.501

Abstract Bovine serum albumin (BSA) glomerulonephritis is a type of immune complex glomerulonephritis that is characterized by a large number of leukocytes infiltrating the kidney. Interleukin (IL)-18, which has potent interferon (IFN)-γ-inducing activities, may play an important role in lymphocyte-mediated inflammatory responses. To investigate the role of IL-18 in BSA glomerulonephritis, we used IL-18R-deficient C57BL/6 mice. Compared with control mice, IL-18R-deficient mice showed a significant reduction of proteinuria, renal pathological findings including glomerular IgG and C3 deposits, and leukocyte infiltrates. Transcripts encoding IFN-γ and tumor necrosis factor (TNF)-α in the kidney were significantly reduced in IL-18R-deficient mice compared with those in control mice. On the other hand, serum anti-BSA Ab was not reduced in IL-18R-deficient mice. We conclude that the blockading of IL-18 signaling in BSA nephritis mice significantly alleviates immune complex renal disorder; this may thus represent a novel approach to the treatment of patients with immune complex nephritis.