title: Immunomodulatory therapeutic effect of glatiramer acetate on several murine models of inflammatory bowel disease.
abstract: Inflammatory bowel disease (IBD) is characterized by detrimental immune reactivity in the gut and imbalance between proinflammatory and anti-inflammatory reactivity. In an attempt to down-regulate colitis, we investigated the effect of the immunomodulator glatiramer acetate (GA, Copaxone, copolymer 1) on two murine models of IBD, chemically induced and spontaneous. Acute experimental colitis of different levels of severity was induced in C57BL/6 mice by dextran sulfate sodium (DSS) administered orally at different concentrations and frequencies. It was manifested in weight loss, intestinal bleeding, and diarrhea, as well as by macroscopic and microscopic colon damage. GA treatment led to amelioration of all of these pathological manifestations, resulting in improved long-term survival. Moreover, even when colitis was induced by three cycles of DSS in this highly susceptible mouse strain, as well as in BALB/c mice that exhibit a chronic disease pattern, a substantial reduction in disease activity and mortality was obtained. GA treatment induced a beneficial effect also in a spontaneous model of colitis developed in the C3H/HeJBir IL-10-deficient mice. The detrimental proinflammatory response manifested by proliferation, tumor necrosis factor-alpha, and interferon-gamma expression was modulated by GA, whereas the regulatory anti-inflammatory transforming growth factor-beta and IL-10 cytokines response was elevated. This was demonstrated on the level of protein secretion in splenocytes and local mesenteric lymphocytes in response to syngeneic colon extract and in the overall response to anti-CD3, as well as on the level of mRNA expression in the colon.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel 76100.
authors.forename: Rina
authors.initials: R
authors.lastname: Aharoni
authors.forename: Basak
authors.initials: B
authors.lastname: Kayhan
authors.forename: Ori
authors.initials: O
authors.lastname: Brenner
authors.forename: Hagit
authors.initials: H
authors.lastname: Domev
authors.forename: Galya
authors.initials: G
authors.lastname: Labunskay
authors.forename: Ruth
authors.initials: R
authors.lastname: Arnon
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D000068717:Glatiramer Acetate; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D010455:Peptides; D000068717:Glatiramer Acetate