Suppression of experimental autoimmune encephalomyelitis by dual cyclo-oxygenase and 5-lipoxygenase inhibition.
The release of leukotriene C4 (LTC4), an important 5-lipoxygenase product of the arachidonic acid metabolism from polymorphonuclear leucocytes (PMNLs) of guinea pigs with experimental allergic encephalomyelitis (EAE), the animal model of MS, has been found to be significantly increased compared with healthy animals. Subsequently, the dual cyclo-oxygenase and 5-lipoxygenase inhibitor BW755C was applied to 15 guinea pigs with EAE. Two control groups (15 each) were treated with the cyclo-oxygenase inhibitor indomethacin or physiological saline, respectively. In the BW755C treated group, no animal developed symptoms of the disease in contrast to, respectively, 5 and 3 animals in the 2 other groups. Histological examination of the CNS revealed a highly significantly lower inflammation score in the BW755C treated animals, and the release of LTC4 from PMNLs was highly significantly decreased in this group compared with each of the others. The findings suggest that the vascular permeability enhancing LTC4 plays a pathogenetic role in EAE and indicate that inhibition of this sulfidopeptide leukotriene suppresses the disease. Therefore, the application of leukotriene inhibitors could contribute to the future treatment of MS.
Prosiegel
M
M
Neurological Departments, Fachklinik Enzensberg, Hopfen am See, West Germany.
Neu
I
I
Mallinger
J
J
Wildfeuer
A
A
Mehlber
L
L
Vogl
S
S
Hoffmann
G
G
Ruhenstroth-Bauer
G
G
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D016861:Cyclooxygenase Inhibitors; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005260:Female; D006168:Guinea Pigs; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles / Q000627:therapeutic use*; D013189:SRS-A / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D013189:SRS-A; D007975:Leukotriene B4; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D001091:Arachidonate Lipoxygenases