Development and validation of a novel IL-10 deficient cell transfer model for colitis.
A number of rodent models for inflammatory bowel disease (IBD) have been developed, but most cannot be used to develop and validate new therapies for IBD. From the models developed, the IL-10 deficient mouse model is the one that results in a disease similar to human IBD; however, in this model, colitis occurs with variable incidence taking 3-4 months to develop. These are serious problems with the model when evaluating a new therapy because of the large-scale experiments required and the difficulty in performing an accurate pharmacological analysis. In this study, the IL-10 deficient mouse model was modified by transferring whole spleen and mesenteric lymph node cells from IL-10 deficient mice to CB-17 SCID mice. In this IL-10 deficient cell transfer model, chronic intestinal inflammation developed in all recipients within 2-3 weeks, which was far earlier than in donor IL-10 deficient mice. The pathological phenotypes were similar to those of IL-10 deficient mice and CD45RBhi T cell-transfer models. In addition, we assessed several agents for inflammatory bowel disease to validate the general utility of this cell transfer model. It is worth noting that TNFR-Ig or prednisolone, which is effective for treatment of patients with severe-fulminant Crohn's disease, markedly attenuated pathological clinical indices in this colitis model, whereas the immunosuppressive agents, azathioprine, tacrolimus, and cyclosporine A produced no significant effect. These results suggest that the IL-10 deficient cell transfer model is a good experimental model to use for developing new and effective therapies for active IBD.
Ikenoue
Yuka
Y
Gastroenterology Research, Drug Discovery Department II, Pharmaceutical Research Laboratories, Pharmaceutical Company, Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki, 210-8681, Japan. yuka_ikenoue@ajinomoto.com
Tagami
Tomoyuki
T
Murata
Masahiro
M
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017690:Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000473:pathology*; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D011239:Prednisolone / Q000494:pharmacology; D015203:Reproducibility of Results; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D011239:Prednisolone