Inhibition of Human and Rat Glial Cell Function by Anti-Inflammatory Cytokines, Antioxidants, and Elevators of cAMP

  • Barbara St. Pierre
  • Joyce L. Wong
  • Jean E. Merrill
Part of the Altschul Symposia Series book series (ALSS, volume 4)


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 (de Waal Melefyt et al., 1991; Khoury et al., 1992; reviewed in Merrill and Benveniste, in press).


Nitric Oxide Experimental Autoimmune Encephalomyelitis Multiple Sclerosis Patient Experimental Allergic Encephalomyelitis Human Glial Cell 
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Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Barbara St. Pierre
    • 1
  • Joyce L. Wong
    • 1
  • Jean E. Merrill
    • 2
  1. 1.Department of NeurologyUCLA School of MedicineLos AngelesUSA
  2. 2.Department of ImmunologyBerlex BiosciencesRichmondUSA

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