title: Amelioration of experimental colitis by Copaxone is associated with class-II-restricted CD4 immune blocking.
abstract: Copaxone modifies TH1 immune response in multiple sclerosis. As Crohn's disease shares TH1 predominance, this study came to investigate the anti-inflammatory response of Copaxone in animal model of colitis.
  
  
  METHODS
  Colitis was induced by intra-rectal instillation of TNBS in 2 animal groups; one of them was daily treated intraperitoneally by 300 mug Copaxone starting 48 h post-colitis induction. Both colitis groups were compared to naive group. Eight male C57Bl6 mice were used in each group. At day 12, distal colon was excised for standard scoring, splenocytes were isolated for FACS and serum cytokines were assessed. Splenocytes were in-vitro-stimulated with colitis protein extracts in the presence or absence of Copaxone. Lymphocytes were blocked by either MHC anti-class I or anti-class II antibodies prior to Copaxone administration.
  
  
  RESULTS
  Copaxone markedly alleviated macro/microscopic colitis scoring as they decreased from 2.9 +/- 1.1/2.6 +/- 0.8 in colitis group to 1.7 +/- 1/1.5 +/- 0.5 in Copaxone-treated mice (P = 0.03/P = 0.008, respectively) compared to 0 +/- 0/1 +/- 0 in naives (P < 0.001/P < 0.01, respectively). CD4 subsets significantly decreased following Copaxone administration as compared to naive mice (P = 0.05). Although Copaxone-treated mice manifested a block of both serum TH1/TH2 responses, only interferon gamma secreting CD4 cells significantly decreased. NK cells tend to increase following colitis induction (P = 0.08), however, they significantly decreased in Copaxone-treated animals (P = 0.006). NK-T followed NK pattern. Using in vitro studies, Copaxone showed amelioration of T-cell proliferation that was significantly blocked when cells were pre-incubated with anti-MHC class II but not class I antibodies.
  
  
  CONCLUSIONS
  Copaxone had class-II-restricted anti-inflammatory effect in our animal colitis model associated with CD4/NK/NKT/TH1/TH2 suppression.
authors.affiliation: Liver Unit, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Chamutal
authors.initials: C
authors.lastname: Gur
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Karussis
authors.forename: Eran
authors.initials: E
authors.lastname: Golden
authors.forename: Sarit
authors.initials: S
authors.lastname: Doron
authors.forename: Yaron
authors.initials: Y
authors.lastname: Ilan
authors.forename: Rifaat
authors.initials: R
authors.lastname: Safadi
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D000068717:Glatiramer Acetate; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate