PT  - JOURNAL ARTICLE
AU  - Rina Aharoni
AU  - Basak Kayhan
AU  - Ori Brenner
AU  - Hagit Domev
AU  - Galya Labunskay
AU  - Ruth Arnon
TI  - Immunomodulatory Therapeutic Effect of Glatiramer Acetate on Several Murine Models of Inflammatory Bowel Disease
AID  - 10.1124/jpet.106.103192
DP  - 2006 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 68--78
VI  - 318
IP  - 1
4099  - http://jpet.aspetjournals.org/content/318/1/68.short
4100  - http://jpet.aspetjournals.org/content/318/1/68.full
SO  - J Pharmacol Exp Ther2006 Jul 01; 318
AB  - 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-α, and interferon-γ expression was modulated by GA, whereas the regulatory anti-inflammatory transforming growth factor-β 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. The American Society for Pharmacology and Experimental Therapeutics