[Effects of neutralizing antibodies on cytokine treatment for anti-GBM nephritis in mouse]. 1996

T Hattori, and N Fujitsuka, and A Kurogi, and S Shindo
Tsumura Co. Ltd., Central Laboratories, New Drug Research, Ibaragi, Japan.

The process of glomerular injury in nephrotoxic serum nephritis (NTN) is dependent on proinflammatory cytokines. In the present investigation, we assessed the actions of neutralizing antibody against IL-1 beta, TNF-alpha, IL-6 and TGF-beta 1 on glomerular injury. Marked increase in IL-1 beta and IL-6 was detected in cultured glomeruli of NTN in mice throughout the experiments from disease induction. Protein of TNF-alpha and TGF-beta 1 also increased in NTN mice 1 day after disease induction. Treatment with either IL-1 beta or TNF-alpha neutralizing antibody reduced proteinuria from 71 +/- 11.2 m g/24 hr to 32.2 +/- 6.0 (P < 0.01). 34.3 +/- 6.8 mg/24 hr (P < 0.01), respectively. Although the effect of IL-6 neutralizing antibody on proteinuria was not remarkable, the decreased creatinine clearance was improved more than that of IL-1 beta or TNF-alpha. Antibody against TGF-beta 1 had no effect on proteinuria and creatinine clearance. Treatments with IL-1 beta, TNF-alpha and IL-6 neutralizing antibodies inhibited glomerular hypercellularity in NTN mice. TGF-beta 1 neutralizing antibody suppressed the index of mesangial matrix expansion. IL-1 beta and TNF-alpha neutralizing antibodies prevented the increase in the number of macrophages in the glomeruli. The number of PCNA positive cells and alpha-smooth muscle actin expression in glomeruli was significantly reduced in the IL-6 neutralizing antibody-treated group. These results confirm the direct involvement of IL-1 beta, TNF-alpha and IL-6 in mouse NTN. We speculate that TGF-beta 1 may inhibit excessive proliferation in glomerular cells.

UI MeSH Term Description Entries
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D007678 Kidney Glomerulus A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue. Glomerulus, Kidney
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D005921 Glomerulonephritis Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY. Bright Disease,Kidney Scarring,Glomerulonephritides,Scarring, Kidney
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000906 Antibodies Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
D001323 Autoantibodies Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them. Autoantibody
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D015850 Interleukin-6 A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS. Hepatocyte-Stimulating Factor,Hybridoma Growth Factor,IL-6,MGI-2,Myeloid Differentiation-Inducing Protein,Plasmacytoma Growth Factor,B Cell Stimulatory Factor-2,B-Cell Differentiation Factor,B-Cell Differentiation Factor-2,B-Cell Stimulatory Factor 2,B-Cell Stimulatory Factor-2,BSF-2,Differentiation Factor, B-Cell,Differentiation Factor-2, B-Cell,IFN-beta 2,IL6,Interferon beta-2,B Cell Differentiation Factor,B Cell Differentiation Factor 2,B Cell Stimulatory Factor 2,Differentiation Factor 2, B Cell,Differentiation Factor, B Cell,Differentiation-Inducing Protein, Myeloid,Growth Factor, Hybridoma,Growth Factor, Plasmacytoma,Hepatocyte Stimulating Factor,Interferon beta 2,Interleukin 6,Myeloid Differentiation Inducing Protein,beta-2, Interferon
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine

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