The transfer of genes encoding immunoregulatory
proteins is a promising new strategy in the treatment of intestinal
inflammation. Previous work has demonstrated that daily systemic
interleukin (IL)-10
therapy is able to prevent disease onset in animal models of
colitis but is not sufficient to treat established disease. This study investigates the therapeutic efficacy of an adenovirus encoding
IL-10 (AdvmuIL-10) in the treatment of experimental
colitis.
Colitis was induced in BALB/c mice by the addition of
dextran sodium sulfate to the
drinking water for 7 days. A single systemic injection of AdvmuIL-10, empty cassette vector (Adv0), or saline vehicle was administered on day 4 after the onset of
colitis. The addition of DSS to the
drinking water led to an acute, dose-dependent
colitis. A single injection of AdvmuIL-10 led to a marked reduction in both stool markers of
inflammation (IL-1beta, IL-6, and TNFRII) and serum
IL-6. Furthermore, the histological
colitis score was significantly reduced in mice receiving AdvmuIL-10 compared to controls (4.9 +/- 1.1 Vs 9.1 +/- 1.2, respectively; P < 0.05). A single systemic injection of AdvmuIL-10 is therapeutic in mice with established DSS
colitis. Gene therapy strategies using adenoviral vectors encoding
IL-10 may prove to be a potent
therapy for chronic
inflammation of the colon such as
Crohn's disease.