title: Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector.
abstract: Genetic deficiency in the expression of interleukin-10 (IL-10) is associated with the onset and progression of experimental inflammatory bowel disease (IBD). The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10), an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate), a common model of colitis. Adenoviral IL-10 (Ad-IL10) transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml) within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS), Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10) gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation.
authors.affiliation: Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, LA 71130-3932, USA. msasaki@lsuhsc.edu
authors.forename: Makoto
authors.initials: M
authors.lastname: Sasaki
authors.forename: J Michael
authors.initials: JM
authors.lastname: Mathis
authors.forename: Merilyn H
authors.initials: MH
authors.lastname: Jennings
authors.forename: Paul
authors.initials: P
authors.lastname: Jordan
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wang
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ando
authors.forename: Takashi
authors.initials: T
authors.lastname: Joh
authors.forename: J Steven
authors.initials: JS
authors.lastname: Alexander