title: TH1/TH2 Cytokine profile in relapsing-remitting multiple sclerosis patients treated with Glatiramer acetate or Natalizumab.
abstract: BACKGROUND
  The balance between T helper cells Th2- and Th1-related cytokines plays a key role in multiple sclerosis (MS). A shift from a Th1 towards a Th2 cytokine profile could have a beneficial effect on the clinical course of the disease. The objective of this study was to assess Th2/Th1 cytokine profile in relapsing-remitting MS (RRMS) patients receiving an immunosuppressive treatment with natalizumab (NAT), or an immunomodulatory treatment with glatiramer acetate (GA) after one year of treatment.
  
  
  METHODS
  This was an observational cross-sectional study. All consecutive patients diagnosed with RRMS who had received GA or NAT for 12 months were included in the study. We determined serum levels of Th1 and Th2 cytokines (interleukin [IL]-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, monocyte chemotactic protein [MCP]-1, tumor-necrosis factor [TNF]-α, interferon [IFN]-γ and granulocyte macrophage colony stimulating factor [GM-CSF]) by flow cytometry. Th2/Th1 bias was defined based on the ratio of IL-4, IL-5, IL-6 or IL-10 Th2 cytokines and proinflammatory INF-γ or TNF-α Th1 cytokines.
  
  
  RESULTS
  Eleven patients under treatment with NAT and 12 patients treated with GA were evaluated. RRMS patients treated with NAT showed significantly higher levels of IL-6 (p < 0.05), MCP-1 (p < 0.01), and GM-CSF (p < 0.05) compared to GA patients after one year of treatment. A trend for increasing of IL-12p70, IL-1b, TNF- α and IFN- γ levels was also found in patients receiving NAT compared to GA patients. IL-4/IFN-γ, IFN-γ/TNF-α and IL-10/IFN-γ ratios as markers of Th2/Th1 ratio were significantly elevated in GA patients compared to those receiving NAT (p < 0.05).
  
  
  CONCLUSIONS
  In conclusion, our findings suggest that GA promotes a superior Th2-biased anti-inflammatory response as compared with NAT in the systemic circulation of RRMS patients. Future studies with larger cohorts will determine whether this immune Th2 shift in GA patients is associated with a beneficial effect on disease outcome.
authors.affiliation: Department of Neurology, Neuroimmunology and Multiple Sclerosis Unit, University Hospital La Paz, Madrid, Spain. orejacbn@gmail.com
authors.forename: Celia
authors.initials: C
authors.lastname: Oreja-Guevara
authors.forename: Jaime
authors.initials: J
authors.lastname: Ramos-Cejudo
authors.forename: Luiz Stark
authors.initials: LS
authors.lastname: Aroeira
authors.forename: Beatriz
authors.initials: B
authors.lastname: Chamorro
authors.forename: Exuperio
authors.initials: E
authors.lastname: Diez-Tejedor
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood* / Q000276:immunology*; D000068717:Glatiramer Acetate; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D000069442:Natalizumab; D010455:Peptides / Q000627:therapeutic use*; D055502:Secondary Prevention; D058408:Th1-Th2 Balance / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D000069442:Natalizumab; D010455:Peptides; D000068717:Glatiramer Acetate