Suppression of experimental allergic encephalomyelitis in the Lewis rat by the matrix metalloproteinase inhibitor Ro31-9790.
Matrix metalloproteinases (MMPs) are implicated in the tissue destruction associated with inflammatory demyelinating diseases such as multiple sclerosis. The effect of a hydroxamate inhibitor of MMPs, Ro31-9790, on inflammatory demyelination was assessed in two acute models of experimental allergic encephalomyelitis (EAE). Daily intraperitoneal injections of Ro31-9790 (50 mg kg-1), beginning either at the time of disease induction or from day 3 post induction, significantly reduced the clinical severity of adoptively transferred EAE. Administration of the inhibitor from the day of induction of active EAE prevented disease onset in 9/10 animals. However, in a repeat study, in which clinical disease was much more severe in the vesicle treated animals, the inhibitor was less effective. Clinical signs and CNS histopathology correlated well, with greater numbers of inflammatory lesions associated with increased disease severity. The present study confirms a role for then MMP cascade in inflammation in EAE.
Hewson
A K
AK
Multiple Sclerosis Laboratory, Institute of Neurology, London, UK.
Smith
T
T
Leonard
J P
JP
Cuzner
M L
ML
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006877:Hydroxamic Acids; D016219:Immunotherapy, Adoptive; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D004676:Myelin Basic Protein / Q000276:immunology; D011480:Protease Inhibitors / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew
D006877:Hydroxamic Acids; D004676:Myelin Basic Protein; D011480:Protease Inhibitors; C097661:Ro 31-9790; D008666:Metalloendopeptidases