Effects of neutralizing antibodies on cytokine treatment for anti-GBM nephritis in mouse

• Published in: Nihon Jinzo Gakkai shi Vol. 38; no. 12; pp. 563 - 570
• Main Authors: KUROGI, Akiko, HATTORI, Tomohisa, FUJITSUKA, Naoki, SHINDO, Shoichiro
• Format: Journal Article
• Language: Japanese
• Published: Japan Japanese Society of Nephrology 1996
• Subjects: Animals; Anti-GBM nephritis, Interleukin-1β, TNF-α, Interleukin-6; Antibodies - immunology; Autoantibodies; Cytokines - immunology; Glomerulonephritis - immunology; Glomerulonephritis - pathology; Interleukin-1 - immunology; Interleukin-6 - immunology; Kidney Glomerulus - immunology; Mice; Mice, Inbred BALB C; Tumor Necrosis Factor-alpha - immunology
• ISSN: 0385-2385; 1884-0728
• DOI: 10.14842/jpnjnephrol1959.38.563

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, 9, TNF-α, IL-6 and TGF-β1 on glomerular injury. Marked increase in IL-1 and IL-6 was detected in cultured glomeruli of NTN in mice throughout the experiments from disease induction. Protein of TNF-α and TGF-$1 also increased in NTN mice 1 day after disease induction. Treatment with either IL-l, S or TNF- a 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 βor TNF-α. Antibody against TGF-β 1 had no effect on proteinuria and creatinine clearance. Treatments with IL-1 β, TNF-α and IL-6 neutralizing antibodies inhibited glomerular hypercellularity in NTN mice. TGF-β1 neutralizing antibody suppressed the index of mesangial matrix expansion. IL-l, 3 and TNF-αneutralizing 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-1β, TNF-αand IL-6 in mouse NTN. We speculate that TGF-β1 may inhibit excessive proliferation in glomerular cells.