ANTISERUM AGAINST TUMOR-NECROSIS-FACTOR-ALPHA AND A PROTEASE INHIBITOR REDUCE IMMUNE GLOMERULAR INJURY

被引:71
作者
HRUBY, ZW
SHIROTA, K
JOTHY, S
LOWRY, RP
机构
[1] MCGILL UNIV,ROYAL VICTORIA HOSP,DEPT MED,MONTREAL H3A 1A1,QUEBEC,CANADA
[2] MCGILL UNIV,ROYAL VICTORIA HOSP,DEPT PATHOL,MONTREAL H3A 1A1,QUEBEC,CANADA
基金
英国医学研究理事会;
关键词
D O I
10.1038/ki.1991.177
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Previous studies in this laboratory have documented tumor necrosis factor alpha (TNF) release by macrophage laden glomeruli in the accelerated autologous form of nephrotoxic serum nephritis (AA-NTSN). We now report that the administration of anti-TNF antiserum to rats with the AA-NTSN reduces albuminuria in a dose related manner (day 8 postinduction) and limits glomerular necrosis (P < 0.05) without affecting the endogenous creatinine clearance (C(Cr)). Protease inhibitors block cytolytic activity of TNF in vitro and reduce glomerular necrosis in experimental nephritis in vivo. The combined administration of anti-TNF antiserum and an amidine-type protease inhibitor (BABIM) to rats with the AA-NTSN caused a greater diminution of albuminuria and histopathology than observed in rats treated with either agent alone, and also prevented the fall in C(Cr) otherwise observed in this model system. Since, in our studies, BABIM did not inhibit cytolytic TNF activity in vitro, we conclude that the effects of combined administration of these two agents are mediated by independent mechanisms. Our results highlight the pathogenic significance of local TNF release in immune renal disease accompanied by prominent glomerular macrophage accumulation.
引用
收藏
页码:43 / 51
页数:9
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