PMID- 15840028
OWN - NLM
STAT- MEDLINE
DCOM- 20050822
LR  - 20131121
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 67
IP  - 5
DP  - 2005 May
TI  - Antibody blockade of TNF-alpha reduces inflammation and scarring in experimental 
      crescentic glomerulonephritis.
PG  - 1812-20
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine 
      produced by macrophages, and by renal mesangial and tubular epithelial cells. It 
      stimulates the release of interleukin (IL)-1beta, monocyte chemoattractant 
      protein-1 (MCP-1), and transforming growth factor-beta (TGF-beta). Blockade of 
      TNF-alpha is currently used clinically in several autoimmune inflammatory 
      diseases. We hypothesised that blocking TNF-alpha with a monoclonal antibody 
      would prevent inflammation and renal fibrosis in crescentic glomerulonephritis. 
      METHODS: Nephrotoxic nephritis was induced in Wistar Kyoto (WKY) rats by 
      intravenous injection of rabbit antirat glomerular basement membrane (GBM) 
      nephrotoxic serum (NTS). Anti-TNF-alpha monoclonal antibody or saline was given 
      intraperitoneally three times per week in four protocols: experiment 1, days 0 to 
      7; experiment 2, days 0 to 14 and days 4 to 14; experiment 3, days 4 to 28; and 
      experiment 4, days 14 to 28. RESULTS: In experiment 1, rats treated from disease 
      induction had less glomerular fibrinoid necrosis and fewer glomerular macrophages 
      at day 7. In experiment 2, rats treated from day 0 or day 4 showed improved renal 
      function, as judged by serum creatinine, with a significant reduction in 
      crescents. In experiment 3, anti-TNF-alpha treatment significantly reduced urine 
      protein to creatinine ratio and urinary MCP-1 levels. Serum creatinine was 
      preserved at both day 14 and day 28. Tubulointerstitial inflammation, glomerular 
      and tubulointerstitial scarring, and markers of fibrosis [alpha-smooth muscle 
      actin (alpha-SMA) and type IV collagen] were significantly less in treated rats 
      at day 28. In experiment 4, serum creatinine was higher and tubulointerstitial 
      scarring was less in delayed-treated animals. CONCLUSION: Neutralization of 
      endogenous TNF-alpha reduces glomerular inflammation, crescent formation, and 
      tubulointerstitial scarring, with preservation of renal function, in experimental 
      crescentic glomerulonephritis. TNF-alpha blockade is effective even when 
      introduced at the time of maximum glomerular inflammation.
FAU - Khan, Sarah B
AU  - Khan SB
AD  - Renal Section and Department of Histopathology, Faculty of Medicine, Imperial 
      College London, Hammersmith Hospital, London, United Kingdom.
FAU - Cook, H Terence
AU  - Cook HT
FAU - Bhangal, Gurjeet
AU  - Bhangal G
FAU - Smith, Jennifer
AU  - Smith J
FAU - Tam, Frederick W K
AU  - Tam FW
FAU - Pusey, Charles D
AU  - Pusey CD
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - AYI8EX34EU (Creatinine)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Basement Membrane/immunology
MH  - Creatinine/blood
MH  - Glomerulonephritis/etiology/immunology/pathology/*therapy
MH  - Kidney Glomerulus/immunology
MH  - Male
MH  - Rabbits
MH  - Rats
MH  - Rats, Inbred WKY
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors
EDAT- 2005/04/21 09:00
MHDA- 2005/08/23 09:00
CRDT- 2005/04/21 09:00
PHST- 2005/04/21 09:00 [pubmed]
PHST- 2005/08/23 09:00 [medline]
PHST- 2005/04/21 09:00 [entrez]
AID - S0085-2538(15)50659-5 [pii]
AID - 10.1111/j.1523-1755.2005.00279.x [doi]
PST - ppublish
SO  - Kidney Int. 2005 May;67(5):1812-20. doi: 10.1111/j.1523-1755.2005.00279.x.