Immunomodulatory therapeutic effect of glatiramer acetate on several murine models of inflammatory bowel disease
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Date
2006
Journal Title
Journal ISSN
Volume Title
Publisher
Journal of Pharmacology and Experimental Therapeutics
Access Rights
info:eu-repo/semantics/openAccess
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- , and interferon- expression
was modulated by GA, whereas the regulatory anti-inflammatory
transforming growth factor- 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.
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Journal or Series
Journal of Pharmacology and Experimental Therapeutics
WoS Q Value
Scopus Q Value
Volume
318
Issue
1
Citation
Aharoni, R. Kayhan, B. Brenner, O. Domev, H. Labunskay, G. Arnon, R. (2006). Immunomodulatory Therapeutic Effect of Glatiramer Acetate on Several Murine Models of Inflammatory Bowel Disease. Journal of Pharmacology and Experimental Therapeutics, 318(1), 68–78.
