PMID- 14993492 OWN - NLM STAT- MEDLINE DCOM- 20041209 LR - 20131121 IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 19 IP - 5 DP - 2004 May TI - Pentoxifylline suppresses renal tumour necrosis factor-alpha and ameliorates experimental crescentic glomerulonephritis in rats. PG - 1106-15 AB - BACKGROUND: Crescentic glomerulonephritis is a rapidly progressive form of glomerulonephritis, but treatment remains non-specific. The methylxanthine derivative pentoxifylline (PTX) is a clinically available phosphodiesterase inhibitor with anti-inflammatory and immunoregulatory activities. This study examined whether PTX has beneficial effects in a rat model of anti-glomerular basement membrane (GBM) crescentic glomerulonephritis. METHODS: Experimental crescentic glomerulonephritis was induced in Wistar rats by intravenous injection of rabbit anti-rat GBM serum and treated with either vehicle (phosphate-buffered saline) or PTX (0.1 g/kg/day) intravenously on a daily basis. Groups of six animals were euthanized at days 3, 7, 14 or 28 after induction of disease. Effects of PTX on renal function, histology and expression of cytokines, chemokines and adhesion molecules were determined. RESULTS: Compared with the vehicle-treated nephritic rats, PTX treatment beginning at the start of the nephritis significantly suppressed mRNA expression of tumour necrosis factor (TNF)-alpha, but not interleukin-1 beta, throughout the course of nephritis. Moreover, PTX decreased renal mRNAs for intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted (RANTES) and osteopontin (OPN) at all time points examined. These effects were associated with a significant inhibition of macrophage and T-cell infiltration, a reduction of 24-h urinary protein excretion (50-75%, P<0.05), an improvement of histological damage including glomerular crescent formation (60-70%, P<0.01) and a decrease of cortical mRNAs for type I (alpha 1) collagen and fibronectin. The efficacy of PTX could also be seen, though to a lesser extent, in rats with established nephritis. CONCLUSIONS: PTX is an effective anti-inflammatory and immunomodulatory agent capable of suppressing rat crescentic glomerulonephritis. Inhibition of renal TNF-alpha, ICAM-1, RANTES, MCP-1 and OPN expression may be a mechanism whereby PTX suppresses progressive renal injury in rat crescentic glomerulonephritis. FAU - Chen, Yung-Ming AU - Chen YM AD - Department of Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Ng, Yee-Yung AU - Ng YY FAU - Lin, Shuei-Liong AU - Lin SL FAU - Chiang, Wen-Chih AU - Chiang WC FAU - Lan, Hui Y AU - Lan HY FAU - Tsai, Tun-Jun AU - Tsai TJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20040219 PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (DNA Primers) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - SD6QCT3TSU (Pentoxifylline) SB - IM MH - Animals MH - DNA Primers MH - Disease Models, Animal MH - Glomerulonephritis/*drug therapy/genetics MH - Macrophages/pathology MH - Male MH - Pentoxifylline/*pharmacology/*therapeutic use MH - Proteinuria MH - RNA, Messenger/genetics MH - Rats MH - Rats, Wistar MH - Reverse Transcriptase Polymerase Chain Reaction MH - T-Lymphocytes/pathology MH - Tumor Necrosis Factor-alpha/drug effects/*genetics EDAT- 2004/03/03 05:00 MHDA- 2004/12/16 09:00 CRDT- 2004/03/03 05:00 PHST- 2004/03/03 05:00 [pubmed] PHST- 2004/12/16 09:00 [medline] PHST- 2004/03/03 05:00 [entrez] AID - gfh127 [pii] AID - 10.1093/ndt/gfh127 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2004 May;19(5):1106-15. doi: 10.1093/ndt/gfh127. Epub 2004 Feb 19.