Amelioration of CR-EAE with lisofylline: effects on mRNA levels of IL-12 and IFN-gamma in the CNS.
CR-EAE is a Th1-mediated inflammatory autoimmune demyelinating disease of the CNS and serves as a model of human multiple sclerosis. Our previous studies have shown the protective effect of orally administered lisofylline in the prevention of active and passively induced acute EAE. In our present studies we have examined the efficacy and mechanism of action of lisofylline on CR-EAE. Lisofylline decreased the number and severity of paralytic attacks in mice with relapsing EAE. The reduction of clinical disease correlated with decreased levels of mRNA levels of IFN-gamma but not of mRNA levels of IL-12. These studies suggest that lisofylline may be an effective therapeutic for established Th1 mediated autoimmune disease and that it acts by blocking IL-12R signaling and not IL-12 production in vivo.
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Department of Neurology, Multiple Sclerosis Research Center, Room 1222, Vanderbilt Stallworth Rehabilitation Hospital, Vanderbilt University Medical Center, 2201 Capers Ave, Nashville, TN 37212, USA.
Cooper
J C
JC
Klaus
S J
SJ
Sriram
S
S
D000818:Animals; D002490:Central Nervous System / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006168:Guinea Pigs; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D010431:Pentoxifylline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma; C025189:lisofylline; D010431:Pentoxifylline