Inhibition of human and rat glial cell function by anti-inflammatory cytokines, antioxidants, and elevators of cAMP

Editors

Bernhard H. J. Juurlink; Richard M. Devon; J. Ronald Doucette; Adil J. Nazarali; David J. Schreyer; Valerie M. K. Verge

Document Type

Chapter

Publication Date

1997

Publication Title

Cell Biology and Pathology of Myelin

Publisher

Springer

Publisher Location

New York

Volume

4

First page number:

265

Last page number:

276

Abstract

There is accumulating evidence for the involvement of tumor necrosis factor alpha (TNFα) and nitric oxide (NO), produced as a consequence of activation of inducible nitric oxide synthase (iNOS), in Multiple Sclerosis (MS). The same evidence has been found in the animal model of MS, experimental allergic encephalomyelitis (EAE). EAE brains and spinal cords have elevated levels of iNOS and NO correlating with the severity and stage of the disease. Aminoguanidine, an inhibitor of iNOS, ameliorates EAE. Inducible NOS mRNA and protein have been detected in MS brain and footprints of NO seen in serum and spinal fluid of MS patients (reviewed in Parkinson et al., in press). TNFa is also elevated in MS patients’ central nervous system (CNS) as well as in EAE, where the interference with the TNFα receptor or TNFa itself antagonizes the disease in the mouse model. The functional removal of macrophages or the pretreatment of EAE animals with Interleukin 4 (IL4), Interleukin 10 (ILIO), or Interleukin 13 (IL13), which downregulate class II major histocompatability molecules, ILl and TNFα, inhibit clinical and histological EAE.

Keywords

Encephalomyelitis; Interleukins; Macrophages; Multiple Sclerosis; Nitric oxide; Nitric oxide synthase; Tumor necrosis factor

Disciplines

Medicine and Health Sciences | Neurology | Nursing

Language

English

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