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 inhibitor thalidomide and the poly(ADP-ribose) polymerase (PARP)-inhibitor nicotinic acid amide (NAA) in male DBA/1 hybird mice suffering from type II 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.
Kröger
H
H
German Rheumatology Research Center Department of Biochemistry Berlin, Germany.
Miesel
R
R
Dietrich
A
A
Ohde
M
M
Rajnavölgyi
E
E
Ockenfels
H
H
D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D001172:Arthritis, Rheumatoid; D002417:Cattle; D003094:Collagen / Q000276:immunology / Q000633:toxicity*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007114:Immunization; D007518:Isoantibodies / Q000097:blood; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000187:drug effects; D009536:Niacinamide / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D016897:Respiratory Burst / Q000187:drug effects; D013792:Thalidomide / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D007518:Isoantibodies; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009536:Niacinamide; D013792:Thalidomide; D003094:Collagen; D019255:NADPH Oxidases