IL-10 gene therapy prevents TNBS-induced colitis.

Abstract

The transfer of genes encoding immunomodulatory proteins to the intestinal mucosa is a promising new approach to the treatment of Crohn's disease (CD). This study investigates the therapeutic efficacy of an adenoviral vector encoding IL-10 (AdvmuIL-10) in experimental colitis. BALB/c mice were treated with a single intravenous injection of AdvmuIL-10, empty cassette virus (Adv0) or PBS prior to the induction of trinitrobenzene sulphonic acid (TNBS) colitis. AdvmuIL-10 treatment prevented the severe loss of body weight associated with TNBS administration. In addition, AdvmuIL-10 therapy led to a significant reduction in both stool markers of inflammation (IL-1beta and TNFR-II) and acute phase response (serum amyloid protein). Finally, the histological scores of mice with TNBS colitis treated with AdvmuIL-10 were significantly lower than Adv0- or PBS-treated controls. The therapeutic efficacy of AdvmuIL-10 was associated with a decrease in the IFN-gamma and IL-6 levels detected in colonic homogenates from mice with TNBS colitis, whereas no effect was observed on cytokine release from stimulated systemic lymphocytes. Thus, AdvmuIL-10 is an effective therapy in the TNBS model of colitis. Gene therapy strategies using adenoviral vectors encoding IL-10 may prove to be a potent therapy for chronic inflammatory conditions such as CD.

• Authors: J Lindsay, C Van Montfrans, F Brennan, S Van Deventer, P Drillenburg, H Hodgson, A Te Velde, M Sol Rodriguez Pena
• Journal: Gene therapy (Gene Ther) Vol. 9 Issue 24 Pg. 1715-21 (Dec 2002) ISSN: 0969-7128 [Print] England
• PMID: 12457286 (Publication Type: Journal Article)

Chemical References

• Interleukin-1
• Interleukin-6
• Serum Amyloid A Protein
• Interleukin-10
• Interferon-gamma
• Trinitrobenzenesulfonic Acid

Topics

• Adenoviridae (genetics)
• Animals
• Colitis (immunology, therapy)
• Colon (immunology)
• Feces (chemistry)
• Genetic Therapy (methods)
• Genetic Vectors (administration & dosage)
• Interferon-gamma (immunology)
• Interleukin-1 (analysis)
• Interleukin-10 (genetics)
• Interleukin-6 (immunology)
• Mice
• Mice, Inbred BALB C
• Serum Amyloid A Protein (analysis)
• Transduction, Genetic (methods)
• Trinitrobenzenesulfonic Acid