SUPPRESSION OF TYPE-II COLLAGEN-INDUCED ARTHRITIS BY N-ACETYL-L-CYSTEINE IN MICE

1. The antiarthritic and anti-inflammatory efficacy of N-acetyl-L-cyst eine (NAC) was tested in male DBA/1 hybrid mice suffering from type II collagen-induced arthritis. Parameters including the arthritis index and the phagocytic responses recorded by chemiluminescence in unsepara ted blood were used for the assessment of disease activity. 2. Mice we re immunized by subdermal injection of bovine type II collagen in Freu nd's complete adjuvant. The treatment with NAC started at day 42 after immunization and was continued over a period of six weeks: in doses r anging up to 50 mg/kg, a dose dependent suppression of arthritis was n oted; between 50 and 200 mg/kg, the inhibition curve had a plateau [ED 50=50 mg/(kg x day)]. 3. The arthritis index correlated positively wit h the generation of chemiluminescence by reactive oxygen species (ROS) produced in neutrophils and monocytes activated by 12-O-tetradecanoyl phorbol 13-acetate. 4. After treatment with 100 mg/kg of NAC from day 42 after immunization over a period of six weeks, the ROS production w as reduced to levels occurring. in whole blood of healthy animals. 5. It is concluded that low molecular-weight antioxidants such as NAC may be adequate for controlling oxidative stress-derived damage in rheuma tic diseases by modulation of ROS dependent signal transduction pathwa ys. (C) 1997 Elsevier Science Inc.