The effects of monoamine reuptake inhibiting antidepressants in experimental allergic neuritis.
Experimental allergic neuritis (EAN) is a CD4+ T cell mediated autoimmune disease that is characterized by inflammation and demyelination affecting the peripheral nervous system (PNS). EAN represents an animal model for the study of the immunopathogenesis, immunoregulation and immunotherapy of human Guillain-Barré syndrome (GBS). Although the pathogenesis of EAN remains an enigma, growing evidence points to a possible involvement of an integrated attack by T cells, B cells and macrophages. Th1 related inflammatory cytokines like interferon-gamma (IFN-gamma), tumour necrosis factor-beta (TNF-beta) and TNF-alpha, IL-6 as well as IL-12 could play a major role in the development of tissue damage in EAN. The monoamine reuptake inhibiting antidepressants show immunomodulatory effects on clinical signs and immune response of EAN. The mechanisms behind the suppressive effect of zimeldine, norzimeldine, clomipramine and imipramine on EAN symptoms may include an action on T cell autoreactivities that are directed against myelin proteins. Suppression may be the net result of local accumulation of 5-HT and noradrenalin in regional lymph nodes and peripheral nerves as well as direct and indirect drug effects on cytokine release by peripheral lymphocytes. These antidepressant drugs also exert modulatory effects on MHC class I and II in EAN rat macrophages even in the absence of IFN-gamma. The modulatory effect of antidepressant drugs on IFN-gamma induced MHC class I and II expression may contribute to their influence on demyelinating autoimmune diseases, and may have implications for their clinical use.
Zhu
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Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
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Bengtsson
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D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D006801:Humans; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D014179:Neurotransmitter Uptake Inhibitors / Q000627:therapeutic use*; D051381:Rats
D000928:Antidepressive Agents; D014179:Neurotransmitter Uptake Inhibitors