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Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
Interleukin 10 gene transfer prevents experimental colitis in rats
G Barbara1, Z Xing, C M Hogaboam
1The Intestinal Disease Research Program, Division of Gastroenterology, Departments of Medicine and Pathology, McMaster University Faculty of Health Sciences, Hamilton Health Sciences Corporation, Hamilton, Ontario, Canada.
Gene therapy using adenovirus-interleukin 10 (IL-10) successfully prevented experimental colitis in rats when administered before disease onset. However, it did not reverse established colitis, indicating a critical window for therapeutic intervention.
Area of Science:
- Gastroenterology
- Gene Therapy
- Immunology
Background:
- Interleukin 10 (IL-10) exhibits anti-inflammatory properties, suggesting its potential for treating inflammatory bowel disease (IBD).
- Previous studies using recombinant IL-10 for IBD treatment yielded inconsistent outcomes.
- IL-10 deficiency in mice leads to colitis, highlighting IL-10's crucial role in gut homeostasis.
Purpose of the Study:
- To investigate the therapeutic efficacy of IL-10 gene overexpression in preventing and treating experimental colitis in rats.
- To determine the optimal timing for IL-10 gene delivery in relation to colitis induction.
Main Methods:
- Adenovirus-mediated gene transfer of the IL-10 gene was performed in rats.
- Gene delivery occurred either 24 hours before or 1 hour after inducing colitis with dinitrobenzene sulphonic acid.
- Colonic damage, inflammation, myeloperoxidase activity, and leukotriene B4 levels were assessed.
Main Results:
- Adenovirus-IL-10 gene transfer elevated serum IL-10 protein levels for up to six days.
- Pre-treatment with IL-10 gene transfer significantly improved macroscopic and histological colitis scores.
- Pre-treatment markedly reduced colonic myeloperoxidase activity and leukotriene B4 concentrations, while post-treatment showed no benefit.
Conclusions:
- Adenovirus-mediated IL-10 gene therapy is effective in preventing experimental colitis in rats.
- Therapeutic intervention with IL-10 gene transfer is time-sensitive, requiring administration before colitis onset.
- This study demonstrates the potential of gene therapy for preventing IBD but not for reversing established disease.
