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The prevention and treatment of murine colitis using gene therapy with adenoviral vectors encoding IL-10

Lindsay, JO; Ciesielski, CJ; Scheinin, T; Hodgson, HJ; Brennan, FM; (2001) The prevention and treatment of murine colitis using gene therapy with adenoviral vectors encoding IL-10. The Journal of Immunology , 166 (12) pp. 7625-7633.

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IL-10-deficient (IL-10(-/-)) mice develop colitis with many similarities to Crohn's disease. Daily IL-10 injections have a short systemic half-life and are unable to induce complete remission in IL-10(-/-) mice with established disease. In this paper, we investigate the duration, potency, and immunogenicity of gene therapy using an adenoviral vector encoding murine IL- 10 (AdvmuIL-10). A single systemic injection of AdvmuIL-10 was sufficient not only to prevent the onset of colitis for at least 10 wk but also to induce clinical and histological remission in mice with established disease. In addition, AdvmuIL-10 diminished the systemic manifestations of disease, including elevated acute-phase proteins, as well as the local consequences of inflammation such as raised stool IL-1 beta concentrations. Both IL-10 protein and the effects of secreted IL-10 were detectable for 10 wk after AdvmuIL-10 injection. Furthermore, the immunoregulatory effect of a single AdvmuIL-10 injection was manifest both by a reduction in TNF-alpha, IFN- gamma, and RANTES release from stimulated splenocyte cultures, and also by a change in the proportion of CD45RB(high/low) lymphocytes in the spleen compared with control mice. The delivery of AdvmuIL-10 resulted in a significantly diminished host antiadenoviral response compared with control adenoviral vectors. Thus, gene therapy strategies using adenoviral vectors encoding immunoregulatory and antiinflammatory cytokines may prove to be a potent approach for the treatment of chronic inflammatory disease. Antiinflammatory cytokine expression protects against immune responses directed at gene vectors

Type: Article
Title: The prevention and treatment of murine colitis using gene therapy with adenoviral vectors encoding IL-10
Additional information: UI - 21286519 LA - eng RN - 0 (Antibodies, Viral) RN - 0 (Genetic Vectors) RN - 0 (Immunosuppressive Agents) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor) RN - 130068-27-8 (Interleukin-10) RN - 82115-62-6 (Interferon Type II) PT - Journal Article DA - 20010606 IS - 0022-1767 SB - AIM SB - IM CY - United States
Keywords: ACTIVE CROHNS-DISEASE, Acute Phase Protein, acute phase proteins, ACUTE-PHASE PROTEIN, Acute-Phase Proteins, adenoviral vector, ADENOVIRAL VECTORS, ANTIINFLAMMATORY CYTOKINES, As, beta, CD4(+) T-CELLS, Chronic, clinical, colitis, COLLAGEN-INDUCED ARTHRITIS, Complete, Concentration, consequences, control, Crohn's disease, culture, CULTURES, cytokine, Cytokines, DELIVERY, disease, DURATION, effects, English, expression, gamma, GENE, Gene Therapy, GENE-THERAPY, HALF LIFE, Half-Life, Host, HUMORAL IMMUNE- RESPONSES, IFN gamma, IFN-GAMMA, IL-1, IL-10, IL1 beta, immune, IMMUNE RESPONSE, IMMUNE RESPONSES, IMMUNE-RESPONSE, IMMUNE-RESPONSES, IMMUNOGENICITY, INDUCE, Inflammation, INFLAMMATORY BOWEL-DISEASE, Inflammatory Disease, INJECTION, Injections, INTESTINAL INFLAMMATION, JUN, local, LYMPHOCYTE, Lymphocytes, MANIFESTATIONS, May, MD, mice, murine, ONSET, PAPER, POTENT, Prevention, PROTECTS, PROTEIN, Proteins, Rantes, RECOMBINANT HUMAN INTERLEUKIN-10, REDUCTION, release, REMISSION, response, RESPONSES, SCID MICE, SINGLE, Spleen, stool, strategies, strategy, SURG, SYSTEMIC, SYSTEMIC MANIFESTATIONS, THERAPIES, therapy, TNF ALPHA, TNF-ALPHA, transgenic mice, treatment, USA, VECTOR, VECTORS, acute phase proteins, Adenoviridae, administration & dosage, AGENT, AGENTS, Animal, antagonists & inhibitors, antibodies, Antibodies, Viral, Antibody, biosynthesis, Blood, Cells, Cultured, cytology, deficiency, Enterocolitis, genetic, Genetic Vectors, genetics, IM, Immunization Schedule, immunology, Immunosuppressive Agent, Immunosuppressive Agents, Intravenous, INTERFERON, Interferon Type II, interleukin 10, Interleukin-10, LA, Lipopolysaccharide, Lipopolysaccharides, Lymphocyte Transformation, Methods, Mice, Inbred C57BL, Inbred DBA, Knockout, necrosis, Neutralization Tests, pharmacology, prevention & control, Rheumatology, secretion, STATE, STATES, Support, Non-U.S.Gov't, therapeutic use, Tumor, tumor necrosis, Tumor Necrosis Factor, TUMOR-NECROSIS-FACTOR, Type II, united, United States, UNITED-STATES, viral
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/156727
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