Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-I0 vector

Makoto Sasaki, James Michael Mathis, Merilyn H. Jennings, Paul Jordan, Yuping Wang, Tomoaki Ando, Takashi Joh, J. Steven Alexander

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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.

Original languageEnglish
Article number13
JournalJournal of Inflammation
Volume2
DOIs
StatePublished - 31 Oct 2005

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Colitis
Interleukin-10
Inflammatory Bowel Diseases
Inflammation
Animals
Gene therapy
Dextran Sulfate
Peritoneum
Peritoneal Cavity
Wounds and Injuries
Adenoviridae
Genetic Therapy
Intestines
Weight Loss
Colon
Anti-Inflammatory Agents
Adhesion
Animal Models
Cytokines
Molecules

Cite this

Sasaki, Makoto ; Mathis, James Michael ; Jennings, Merilyn H. ; Jordan, Paul ; Wang, Yuping ; Ando, Tomoaki ; Joh, Takashi ; Alexander, J. Steven. / Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-I0 vector. In: Journal of Inflammation. 2005 ; Vol. 2.
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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.",
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Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-I0 vector. / Sasaki, Makoto; Mathis, James Michael; Jennings, Merilyn H.; Jordan, Paul; Wang, Yuping; Ando, Tomoaki; Joh, Takashi; Alexander, J. Steven.

In: Journal of Inflammation, Vol. 2, 13, 31.10.2005.

Research output: Contribution to journalArticle

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