Enteral immunotherapy in the treatment of chronic enterocolitis in interleukin-10-deficient mice.
OBJECTIVE
Transgenic IL-10-deficient mice (IL-10 ko mice) spontaneously develop a chronic inflammatory bowel disease that is reminiscent of Crohn's disease. In a randomized, prospective, comparative study, we evaluated the effect of local, endoluminal immunotherapy by duodenal injection of mouse recombinant IL-10 (rm IL-10), in IL-10 ko mice with chronic enterocolitis; the first of its kind.


METHODS
Sixteen IL-10 ko mice received a monoinjection of rm IL-10 into the duodenum while a control group of 16 IL-10 ko mice received an injection of physiological saline. Histology of the entire bowel and plasma concentrations of IL-4, IL-6, IL-10, tumor necrosis factor-alpha, and interferon-gamma were analyzed on the 3rd or 7th postoperative day.


RESULTS
The histological features of the specimens from IL-10 ko mice were, non-specific, segmentary and located mainly in the ileum. Lesions were of more significance in mice injected with physiological saline than in those receiving IL-10 in the proximal ileum, near to the site of injection. Plasma concentrations of IL-6 were higher in IL-10 ko mice than in the control group.


CONCLUSIONS
This study confirms that there is hyperproduction of Th1 cytokines in IL-10 ko mice and also suggests that endoluminal administration of IL-10 may be envisaged for the treatment or prevention of enterocolitis.
Glehen
Olivier
O
Surgical Department, Centre Hospitalo-Universitaire Lyon-Sud, Laboratoire Hyperthermie-Oncologie EA 643, Université Lyon 1, France.
Mithieux
François
F
Traverse-Glehen
Alexandra
A
Isaac
Sylvie
S
Bienvenu
Jacques
J
François
Yves
Y
Chung
Raymond
R
Gilly
François-Noël
FN
D000818:Animals; D003424:Crohn Disease / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004386:Duodenum; D004760:Enterocolitis / Q000276:immunology* / Q000473:pathology; D005260:Female; D007082:Ileum / Q000276:immunology / Q000473:pathology; D007167:Immunotherapy; D007267:Injections; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000172:deficiency* / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D016753:Interleukin-10