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.