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.

• Authors: Yuval Sagiv, Ayelet Kaminitz, Haya Lorberboum-Galski, Nadir Askenasy, Shai Yarkoni
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1173 Pg. 791-7 (Sep 2009) ISSN: 1749-6632 [Electronic] United States
• PMID: 19758230 (Publication Type: Journal Article)

Chemical References

• Forkhead Transcription Factors
• Foxp3 protein, mouse
• Interleukin-2
• Interleukin-2 Receptor alpha Subunit
• Recombinant Fusion Proteins
• Dextran Sulfate
• Caspase 3

Topics

• Animals
• Body Weight (drug effects)
• CD4-Positive T-Lymphocytes (cytology, drug effects, metabolism)
• Caspase 3 (genetics, metabolism)
• Colitis (chemically induced, prevention & control)
• Dextran Sulfate
• Forkhead Transcription Factors (metabolism)
• Injections, Intravenous
• Interleukin-2 (genetics, metabolism)
• Interleukin-2 Receptor alpha Subunit (metabolism)
• Mice
• Mice, Inbred BALB C
• Recombinant Fusion Proteins (administration & dosage, metabolism, pharmacology)
• Spleen (cytology, drug effects, metabolism)
• Time Factors
• Treatment Outcome