SYNERGISTIC EFFECTS OF THALIDOMIDE AND POLY(ADP-RIBOSE) POLYMERASE INHIBITION ON TYPE-II COLLAGEN-INDUCED ARTHRITIS IN MICE

The present study investigates synergistic effects of the TNF-alpha in hibitor thalidomide and the poly(ADP-ribose) polymerase (PARP)-inhibit or nicotinic acid amide (NAA) in male DBA/1 hybrid mice suffering from type 11 collagen-induced arthritis. Parameters including the arthriti s index, chemiluminescence and anti-collagen antibody titers were used for the assessment of disease activity: The disease courses demonstra ted clearly an inhibitory effect of thalidomide. NAA inhibited establi shed collagen arthritis in a dose-dependent manner. The combined appli cation of thalidomide and NAA caused a powerful synergistic inhibition of arthritis. Furthermore, thalidomide and NAA were tested ex vivo fo r their inhibition of the NADPH oxidase-dependent generation of reacti ve oxygen species by activated neutrophils and monocytes in unseparate d human blood. Our data show that type II collagen-induced arthritis c an be suppressed by the simultaneous inhibition of TNF-alpha, PARP, an d NADPH oxidase.