Deletion of IL-18 receptor ameliorates renal injury in bovine serum albumin-induced glomerulonephritis.
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.
Sugiyama
Masafumi
M
Department of Nephrology and Rheumatology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
Kinoshita
Koji
K
Kishimoto
Kazuya
K
Shimazu
Hideki
H
Nozaki
Yuji
Y
Ikoma
Shinya
S
Funauchi
Masanori
M
D000818:Animals; D000936:Antigen-Antibody Complex; D005921:Glomerulonephritis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011507:Proteinuria / Q000139:chemically induced; D012333:RNA, Messenger / Q000032:analysis; D053724:Receptors, Interleukin-18 / Q000172:deficiency* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012710:Serum Albumin, Bovine / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000936:Antigen-Antibody Complex; D012333:RNA, Messenger; D053724:Receptors, Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma