A fusion protein composed of IL-2 and caspase-3 ameliorates the outcome of experimental inflammatory colitis.

Abstract:

:Targeted depletion of immune cells expressing the interleukin-2 (IL-2) receptor can exacerbate inflammatory bowel disease (IBD) through elimination of regulatory T (Treg) cells, or ameliorate its course by depletion of cytotoxic cells. To answer this question we used a fusion protein composed of IL-2 and caspase-3 (IL2-cas) in an experimental model of DSS-induced toxic colitis. In a preventive setting, co-administration of DSS with a daily therapeutic dose of IL2-cas for seven days improved all disease parameters. Although CD4(+)CD25(+) T cells were depleted in the mesenteric lymph nodes, a fractional increase in CD4(+)FoxP3(+) T cells was observed in the spleen. Likewise, IL2-cas therapy improved the outcome of established disease in a chronic model of colitis. These data demonstrate that therapies that use IL-2 as a targeting moiety exert a protective effect over the colon under conditions of inflammation. The efficacy of IL-2-targeted therapy is attributed to reduced activity of reactive T cells, which ameliorates the secondary inflammatory infiltration. IL2-cas evolves as a potential therapeutic tool in IBD.

journal_name

Ann N Y Acad Sci

authors

Sagiv Y,Kaminitz A,Lorberboum-Galski H,Askenasy N,Yarkoni S

doi

10.1111/j.1749-6632.2009.04877.x

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

791-7

eissn

0077-8923

issn

1749-6632

pii

NYAS4877

journal_volume

1173

pub_type

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