Aggravation of experimental allergic encephalomyelitis (EAE) by administration of nitric oxide (NO) synthase inhibitors

• Published in: Clinical and experimental immunology 1996-03, Vol.103 (3), p.467-474
• Main Authors: RUULS, S. R., LINDEN, S. VAN DER, SONTROP, K., HUITINGA, I., DIJKSTRA, C. D.
• Format: Article
• Language: English
• Subjects: Animals; Arginine - analogs & derivatives; Arginine - toxicity; Biological and medical sciences; Brain - cytology; Cells, Cultured; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - chemically induced; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - toxicity; experimental allergic encephalomyelitis; Experimental and animal immunopathology. Animal models; Female; Guinea Pigs; Immunopathology; macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Male; Medical sciences; NG-Nitroarginine Methyl Ester; Nitric Oxide - biosynthesis; Nitric Oxide - immunology; nitric oxide nitric oxide synthase inhibitors; Nitric Oxide Synthase - antagonists & inhibitors; Original; Rats; Rats, Inbred Lew
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.1996.tb08304.x

SUMMARY 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 Nw‐nitro‐L‐arginine‐methylester or NG‐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.