title: Diazepam Inhibits Proliferation of Lymph Node Cells Isolated from Rats with Experimental Autoimmune Encephalomyelitis.
abstract: OBJECTIVE
  Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease with similarities to human multiple sclerosis involving peripheral activation of autoreactive T cells which infiltrate the central nervous system and react to self antigens leading to damage. In previous studies, we have demonstrated that treatment with diazepam decreases the incidence and histological signs associated with the disease and diminishes immunological responses. The aim of the present work was to evaluate direct effects of diazepam on isolated T cells involved in immune responses during the development of EAE.
  
  
  METHODS
  Animals were sensitized with whole myelin to induce EAE and sacrificed during the acute phase of the disease. In mononuclear cells isolated from popliteal lymph nodes, cell viability, apoptosis induction, proliferation and cytokine production were evaluated.
  
  
  RESULTS
  Diazepam did not have a toxic or proapoptotic effect on the cells, at least up to the concentration of 25 μM, but proliferation, CD8+ T-cell activation and proinflammatory cytokine production were dose-dependently decreased.
  
  
  CONCLUSIONS
  Diazepam has a direct inhibitory effect on the proliferation and activation of T lymphocytes isolated from the main lymphoid organ involved in disease onset and this could be one of the mechanisms that contribute to the beneficial effect previously observed with diazepam in vivo during EAE development.
authors.affiliation: Departamento de Química Biológica, Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC, UNC-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Fernández Hurst
authors.forename: Mario J
authors.initials: MJ
authors.lastname: Bibolini
authors.forename: German A
authors.initials: GA
authors.lastname: Roth
mesh_terms: D000759:Adjuvants, Anesthesia / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008198:Lymph Nodes / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000759:Adjuvants, Anesthesia; D017304:Annexin A5; D016207:Cytokines; D003975:Diazepam