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Murine Colitis Modeling using Dextran Sulfate Sodium DSS
08:39

Murine Colitis Modeling using Dextran Sulfate Sodium DSS

Published on: January 19, 2010

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Intravenous immunoglobulin (IVIg) or IVIg-treated macrophages reduce DSS-induced colitis by inducing macrophage IL-10

Lisa K Kozicky1, Susan C Menzies1, Naomi Hotte2

  • 1Department of Pediatrics, Division of Gastroenterology, BC Children's Hospital and the University of British Columbia, Vancouver, British Columbia, Canada.

European Journal of Immunology
|May 5, 2019
PubMed

Intravenous immunoglobulin (IVIg) is used to treat immune-mediated diseases but its mechanism of action is poorly understood. We have reported that co-treatment with IVIg and lipopolysaccharide activates macrophages to produce large amounts of anti-inflammatory IL-10 in vitro. Thus, we asked whether IVIg-treated macrophages or IVIg could reduce intestinal inflammation in mice during dextran sulfate sodium (DSS)-induced colitis by inducing macrophage IL-10 production in vivo. Adoptive transfer of IVIg-treated macrophages reduces intestinal inflammation in mice and collagen accumulation post-DSS. IVIg treatment also reduces DSS-induced intestinal inflammation and its activity is dependent on the Fc portion of the antibody. Ex vivo, IVIg induces IL-10 production and reduces IL-12/23p40 and IL-1β production in colon explant cultures. Co-staining tissues for mRNA, we demonstrate that macrophages are the source of IL-10 in IVIg-treated mice; and using IL-10-GFP reporter mice, we demonstrate that IVIg induces IL-10 production by intestinal macrophages. Finally, IVIg-mediated protection is lost in mice deficient in macrophage IL-10 production (LysMcre+/- IL-10fl/fl mice). Together, our data demonstrate a novel, in vivo mechanism of action for IVIg. IVIg-treated macrophages or IVIg could be used to treat people with intestinal inflammation and may be particularly useful for people with inflammatory bowel disease, who are refractory to therapy.

Keywords:
DSS-induced colitisIL-10IVIginflammatory bowel diseasemacrophage

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