title: IL-6 stimulates intestinal epithelial proliferation and repair after injury.
abstract: IL-6 is a pleiotropic cytokine often associated with inflammation. Inhibition of this pathway has led to successful treatment of rheumatoid arthritis, but one unforeseen potential complication of anti-IL-6 therapy is bowel perforation. Within the intestine, IL-6 has been shown to prevent epithelial apoptosis during prolonged inflammation. The role of IL-6 in the intestine during an initial inflammatory insult is unknown. Here, we evaluate the role of IL-6 at the onset of an inflammatory injury. Using two murine models of bowel injury - wound by biopsy and bacterial triggered colitis - we demonstrated that IL-6 is induced soon after injury by multiple cell types including intraepithelial lymphocytes. Inhibition of IL-6 resulted in impaired wound healing due to decreased epithelial proliferation. Using intestinal tissue obtained from patients who underwent surgical resection of the colon due to traumatic perforation, we observed cells with detectable IL-6 within the area of perforation and not at distant sites. Our data demonstrate the important role of IL-6 produced in part by intraepithelial lymphocytes at the onset of an inflammatory injury for epithelial proliferation and wound repair.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Kristine A
authors.initials: KA
authors.lastname: Kuhn
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Manieri
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Ta-Chiang
authors.initials: TC
authors.lastname: Liu
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Stappenbeck
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001706:Biopsy; D049109:Cell Proliferation / Q000235:genetics*; D003092:Colitis / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics*; D007413:Intestinal Mucosa / Q000254:growth & development / Q000293:injuries / Q000378:metabolism*; D007422:Intestines / Q000254:growth & development / Q000293:injuries; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing / Q000235:genetics
chemical_list: D015850:Interleukin-6