title: IL-10 gene therapy is therapeutic for dextran sodium sulfate-induced murine colitis.
abstract: The transfer of genes encoding immunoregulatory proteins is a promising new strategy in the treatment of intestinal inflammation. Previous work has demonstrated that daily systemic interleukin (IL)-10 therapy is able to prevent disease onset in animal models of colitis but is not sufficient to treat established disease. This study investigates the therapeutic efficacy of an adenovirus encoding IL-10 (AdvmuIL-10) in the treatment of experimental colitis. Colitis was induced in BALB/c mice by the addition of dextran sodium sulfate to the drinking water for 7 days. A single systemic injection of AdvmuIL-10, empty cassette vector (Adv0), or saline vehicle was administered on day 4 after the onset of colitis. The addition of DSS to the drinking water led to an acute, dose-dependent colitis. A single injection of AdvmuIL-10 led to a marked reduction in both stool markers of inflammation (IL-1beta, IL-6, and TNFRII) and serum IL-6. Furthermore, the histological colitis score was significantly reduced in mice receiving AdvmuIL-10 compared to controls (4.9 +/- 1.1 Vs 9.1 +/- 1.2, respectively; P < 0.05). A single systemic injection of AdvmuIL-10 is therapeutic in mice with established DSS colitis. Gene therapy strategies using adenoviral vectors encoding IL-10 may prove to be a potent therapy for chronic inflammation of the colon such as Crohn's disease.
authors.affiliation: Department of Gastroenterology, St Mark's Hospital, the North West London NHS Trust, Harrow, Middlesex, UK. j.lindsay@doctors.org.uk
authors.forename: J O
authors.initials: JO
authors.lastname: Lindsay
authors.forename: A
authors.initials: A
authors.lastname: Sandison
authors.forename: P
authors.initials: P
authors.lastname: Cohen
authors.forename: F M
authors.initials: FM
authors.lastname: Brennan
authors.forename: H J F
authors.initials: HJ
authors.lastname: Hodgson
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D016264:Dextran Sulfate; D016503:Drug Delivery Systems; D005260:Female; D005822:Genetic Vectors / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D016753:Interleukin-10; D016264:Dextran Sulfate