Local delivery of adenoviral vectors encoding murine interleukin 10 induces colonic interleukin 10 production and is therapeutic for murine colitis

Introduction: Interleukin 10 knockout (IL-10−/−) mice spontaneously develop a Th1 T cell mediated colitis with many similarities to Crohn’s disease. Daily injections of IL-10 are unable to induce remission in mice with established disease. In contrast, we have shown previously that intravenous administration of adenoviral vectors encoding IL-10 (AdvmuIL-10) induces hepatic IL-10 release and leads to long term disease suppression with profound systemic immunoregulatory changes. Aims: To determine whether rectal delivery of AdvmuIL-10 induces localised colonic IL-10 expression without systemic immune suppression, and assess its therapeutic efficacy in IL-10−/− mice with established colitis. Results: A single rectal infusion of 5×108 PFU AdvmuIL-10 to 10 week IL- 10−/− mice resulted in a median level of 27.3 pg/mg IL-10 in colonic homogenates harvested one week later. IL-10−/− mice with established colitis treated with an enema of 5×108 PFU AdvmuIL-10 entered clinical and histological remission whereas empty cassette adenovirus (Adv0) or phosphate buffered saline (PBS) treated mice developed progressive disease. After four weeks, the histological score of AdvmuIL-10 treated mice (4.4 (1.5)) was significantly lower than that of Adv0 (11.1 (1.1); p