Suppression of experimental autoimmune neuritis by the oxygen radical scavengers superoxide dismutase and catalase.
Macrophages have been implicated in myelin damage in experimental autoimmune neuritis (EAN). We examined a possible pathogenetic role of toxic oxygen species elaborated by macrophages in EAN by administering oxygen radical scavengers. Early treatment of rats with either catalase or superoxide dismutase (10,000 U/kg/day) protected animals from the development of EAN. Treatment delayed until there was clinical manifestation of EAN (day 13) still markedly attenuated the severity of the disease, as evidenced by clinical assessment, electrophysiological studies, and morphological observation. In cell culture, macrophages from sham-treated controls generated heightened oxidative metabolic responses indicating in vivo macrophage activation. Addition of catalase or superoxide dismutase abrogated or diminished chemiluminescence and production of reactive oxygen intermediates by macrophages ex vivo. Our findings underscore the importance of macrophages in EAN and provide evidence that, in this model, macrophage-derived reactive oxygen intermediates contribute to damage of the myelin sheath.
Hartung
H P
HP
Department of Neurology, University of Düsseldorf, West Germany.
Schäfer
B
B
Heininger
K
K
Toyka
K V
KV
D000818:Animals; D002374:Catalase / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000627:therapeutic use*; D013997:Time Factors
D002374:Catalase; D013482:Superoxide Dismutase