Exacerbation of lymphocytic choriomeningitis in mice treated with the inducible nitric oxide synthase inhibitor aminoguanidine.
To elucidate the possible involvement of the inducible nitric oxide synthase (iNOS) and NO in the development of lymphocytic choriomeningitis (LCM), the consequences of inhibition of iNOS by the inhibitor aminoguanidine was examined in mice following intracerebral infection with LCM virus (LCMV). Aminoguanidine administration to mice infected with LCMV completely blocked increased plasma nitrate/nitrite levels and led to increased proinflammatory cytokine gene expression at early stages of lesion development in the brain, enhanced clinical severity and decreased survival time. The levels of LCMV recovered from the brain of aminoguanidine treated mice did not differ from those in infected control mice. These findings argue against either an anti-viral or pathogenic role of NO in LCM but rather suggest a possible protective action of this mediator.
Campbell
I L
IL
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA. icamp@scripps.edu
D000818:Animals; D001921:Brain / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D008216:Lymphocytic Choriomeningitis / Q000382:microbiology / Q000503:physiopathology*; D008217:Lymphocytic choriomeningitis virus; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D009573:Nitrites / Q000097:blood
D016207:Cytokines; D006146:Guanidines; D009566:Nitrates; D009573:Nitrites; D019001:Nitric Oxide Synthase; C004479:pimagedine