Therapeutic effects of 15-deoxyspergualin in acute and chronic relapsing experimental allergic encephalomyelitis (EAE) as models for multiple sclerosis (MS).
Experimental allergic encephalomyelitis (EAE) is an inflammatory and paralytic auto-immune disease of the central nervous system (CNS) resulting from the sensitization of susceptible laboratory animals with whole brain homogenate, lyophilized spinal cord or heterologous myelin basic protein (MBP) in complete Freunds adjuvant (cFA). Acute EAE generally presents as a monophasic disease that produces perivascular inflammation and sometimes small areas of demyelination. The chronic relapsing form of EAE in particular offers important similarities to the human disease multiple sclerosis (MS). Due to its immunosuppressive mode of action, the authors wished to examine the therapeutic effects of 15-deoxyspergualin (15-DOS) in the two models of acute and chronic relapsing EAE in Lewis rats. In the first model, sensitization of adult rats (8-12 weeks of age) with guinea pig spinal cord in cFA results in an acute clinical episode of severe EAE, and by day 17 all animals died. Lewis rats treated with 15-DOS showed a delayed and reduced onset of clinical symptoms and even low amounts of the drug prevented mortality. The protection afforded by 15-DOS was long-lasting and no subsequent relapse has been observed. On rechallenging, such convalescent rats were totally resistant to re-induction of the disease. Passive transfer of EAE to naive Lewis rats was possible with encephalitogenic (antigen-specific primed) spleen cells from diseased control animals but could be prevented by fresh 15-DOS treatment. Passive transfer of acute EAE was suppressed when spleen cells from diseased Lewis rats but 15-DOS-treated animals were used.(ABSTRACT TRUNCATED AT 250 WORDS)
Schorlemmer
H U
HU
Research Laboratories, Behringwerke AG, Marburg Lahn, Germany.
Seiler
F R
FR
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005260:Female; D006146:Guanidines / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy; D051381:Rats; D011917:Rats, Inbred Lew; D012008:Recurrence
D006146:Guanidines; D007166:Immunosuppressive Agents; C037258:gusperimus