| First Author | Kozicky LK | Year | 2019 |
| Journal | Eur J Immunol | Volume | 49 |
| Issue | 8 | Pages | 1251-1268 |
| PubMed ID | 31054259 | Mgi Jnum | J:281734 |
| Mgi Id | MGI:6379527 | Doi | 10.1002/eji.201848014 |
| Citation | Kozicky LK, et al. (2019) Intravenous immunoglobulin (IVIg) or IVIg-treated macrophages reduce DSS-induced colitis by inducing macrophage IL-10 production. Eur J Immunol 49(8):1251-1268 |
| abstractText | 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-1beta 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-10(fl/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. |
