Aggravation of experimental allergic encephalomyelitis (EAE) by administration of nitric oxide (NO) synthase inhibitors.
Macrophages constitute a large proportion of the inflammatory cells that infiltrate the central nervous system (CNS) of animals with EAE. Through the production of inflammatory mediators these infiltrating macrophages can contribute to the regulation of the immune reaction within the CNS, that eventually results in neurological deficits associated with EAE. NO, a free radical produced by macrophages and other cell types, has been put forward as such an immune mediator. In the present study we show that macrophages isolated from the CNS of Lewis rats with clinical signs of EAE produce elevated amounts of NO. We treated rats, in which EAE was induced, with N(omega) -nitro-L-arginine-methylester or N(g)-monomethyl-L-arginine, inhibitors of NO synthase, either systemically via intraperitoneal injection, or intracerebrally via a cannula placed in the lateral ventricle. Both treatments resulted in a marked aggravation of clinical signs of EAE. These data point to an important role of NO, produced by infiltrating macrophages, as an immune-suppressor in the disease process during EAE.
Ruuls
S R
SR
Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
Van Der Linden
S
S
Sontrop
K
K
Huitinga
I
I
Dijkstra
C D
CD
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000633:toxicity; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced* / Q000276:immunology* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D006168:Guinea Pigs; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D011917:Rats, Inbred Lew
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester