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

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)-gamma-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-gamma and tumor necrosis factor (TNF)-alpha 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.

• Authors: Masafumi Sugiyama, Koji Kinoshita, Kazuya Kishimoto, Hideki Shimazu, Yuji Nozaki, Shinya Ikoma, Masanori Funauchi
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 128 Issue 1 Pg. 103-8 (Jul 2008) ISSN: 1521-7035 [Electronic] United States
• PMID: 18462998 (Publication Type: Journal Article)

Chemical References

• Antigen-Antibody Complex
• RNA, Messenger
• Receptors, Interleukin-18
• Tumor Necrosis Factor-alpha
• Serum Albumin, Bovine
• Interferon-gamma

Topics

• Animals
• Antigen-Antibody Complex
• Glomerulonephritis (chemically induced, metabolism, pathology)
• Immunohistochemistry
• Interferon-gamma (biosynthesis)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Proteinuria (chemically induced)
• RNA, Messenger (analysis)
• Receptors, Interleukin-18 (deficiency, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Serum Albumin, Bovine (toxicity)
• Tumor Necrosis Factor-alpha (biosynthesis)