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Third-party-funded project

Title:
The role of NO synthases in the pathogenesis of experimental autoimmune encephalomyelitis

Project management at the University of Würzburg:

Participating scientists:

Abstract:
Experimental autoimmune encephalomyelitis (EAE) is a model of some pathophysiological aspects of multiple sclerosis. We examined the role of nitric oxide (NO) in the pathogenesis of EAE by using the DA rat and mice with a targeted deletion of the cytokine-inducible NO synthase (iNOS-/- mice). We found enhanced expression of iNOS in DA rat EAE. This had a disease-ameliorating effect, since the pharmacological blockade of iNOS in the DA rat with aminoguanidine led to increased disease severity. In iNOS-/- mice, EAE was enhanced in comparison to wildtype mice. This was caused by an increased production of proinflammatory cytokines like interferon-gamma and tumor necrosis factor alpha. Our experiments show that the synthesis of NO had disease-suppressing effects in two different animal models of EAE. Pharmacological blockade of iNOS in MS patients should therefore be viewed with caution.

Key words:
    nitric oxide
    multiple sclerosis
    autoimmunity

Projekt period: from 01.2000 to 08.2001

Preceding project:
IZKF 1995-1999 Projekt C4: Rolle der NO Synthase bei der experimentellen autoimmunen Enzephalomyelitis und Neuritis

Publications: