IL-10 gene therapy prevents TNBS-induced colitis.
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.
Lindsay
J
J
The Kennedy Institute of Rheumatology, Imperial College School of Medicine, London, UK.
Van Montfrans
C
C
Brennan
F
F
Van Deventer
S
S
Drillenburg
P
P
Hodgson
H
H
Te Velde
A
A
Sol Rodriguez Pena
M
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003092:Colitis / Q000276:immunology / Q000628:therapy*; D003106:Colon / Q000276:immunology; D005243:Feces / Q000737:chemistry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D007371:Interferon-gamma / Q000276:immunology; D007375:Interleukin-1 / Q000032:analysis; D016753:Interleukin-10 / Q000235:genetics*; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D000685:Serum Amyloid A Protein / Q000032:analysis; D014161:Transduction, Genetic / Q000379:methods; D014302:Trinitrobenzenesulfonic Acid
D007375:Interleukin-1; D015850:Interleukin-6; D000685:Serum Amyloid A Protein; D016753:Interleukin-10; D007371:Interferon-gamma; D014302:Trinitrobenzenesulfonic Acid