Synergistic effects of thalidomide and poly(ADP-ribose) polymerase inhibition on type II collagen-induced arthritis in mice

被引:28
作者
Kroger, H
Miesel, R
Dietrich, A
Ohde, M
Rajnavolgyi, E
Ockenfels, H
机构
[1] UNIV OTAGO, DEPT BIOCHEM, DUNEDIN, NEW ZEALAND
[2] UNIV ULM, DEPT PHYSIOL CHEM, W-7900 ULM, GERMANY
关键词
D O I
10.1007/BF01487406
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The present study investigates synergistic effects of the TNF-alpha inhibitor thalidomide and the poly(ADP-ribose) polymerase (PARP)-inhibitor nicotinic acid amide (NAA) in male DBA/1 hybrid mice suffering from type 11 collagen-induced arthritis. Parameters including the arthritis index, chemiluminescence and anti-collagen antibody titers were used for the assessment of disease activity: The disease courses demonstrated clearly an inhibitory effect of thalidomide. NAA inhibited established collagen arthritis in a dose-dependent manner. The combined application of thalidomide and NAA caused a powerful synergistic inhibition of arthritis. Furthermore, thalidomide and NAA were tested ex vivo for their inhibition of the NADPH oxidase-dependent generation of reactive oxygen species by activated neutrophils and monocytes in unseparated human blood. Our data show that type II collagen-induced arthritis can be suppressed by the simultaneous inhibition of TNF-alpha, PARP, and NADPH oxidase.
引用
收藏
页码:203 / 215
页数:13
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