title: Benign multiple sclerosis is characterized by a stable neuroimmunologic network.
abstract: OBJECTIVE
  Patients diagnosed with multiple sclerosis (MS) but without disability (Expanded Disability Status Scale score <2) form a specific group within those patients suffering from relapsing-remitting MS. Several neuroimmunologic effectors, including cytokines and melatonin, are known for their influence on the initiation of relapses and progression of the disease.
  
  
  METHODS
  We evaluated 41 female patients with benign MS with respect to their clinical course, treatments and neuroimmunological parameters, including cytokines and melatonin. One subgroup was followed up for 7 years, and another group was evaluated during acute clinical relapse.
  
  
  RESULTS
  The benign MS course in this homogeneous group of young patients was demonstrated by mild disease progression in 16% over 7 years. Initially, patients treated with azathioprine (AZA) revealed significantly reduced melatonin serum levels (p = 0.04) compared to untreated patients, but not at follow-up. During acute relapse, treatment with corticosteroids (CS) resulted in increased levels of type 2 cytokines as well as reduced type 1 cytokine levels.
  
  
  CONCLUSIONS
  Our study supports the functional role of CS acting as an antiinflammatory protagonist during MS relapse, by inducing a shift towards predominance of type 2 cytokines. AZA showed a more subtle modulation of immune functions, reflected by reduced levels of the immune active hormone melatonin. During follow-up, it became apparent that stabilized levels of the interacting Th1/Th2-derived cytokines and melatonin are maintained in concordance with the benign course of MS. These findings are in accordance with the hypothesis that benign MS is characterized by a balanced cytokine and neuroendocrine network, which is supported by immune-modulating therapies.
authors.affiliation: Department of Neurology, University Hospital Essen, Essen, Germany. clausgert.haase.ch@bayer-ag.de
authors.forename: Claus G
authors.initials: CG
authors.lastname: Haase
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Faustmann
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008550:Melatonin / Q000097:blood; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000276:immunology*; D012075:Remission, Spontaneous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D008550:Melatonin; D001379:Azathioprine