IngentaConnect A novel autoimmune pancreatitis model in MRL mice treated with po...

Authors: QU, W.-M.; MIYAZAKI, T.; TERADA, M.; OKADA, K.; MORI, S.¹; KANNO, H.²; NOSE, M.

Source: Clinical & Experimental Immunology, Volume 129, Number 1, July 2002 , pp. 27-34(8)

Abstract:

SUMMARY

In this study we established a new animal model for exploring the pathogenesis of autoimmune pancreatitis. We have found previously that MRL/Mp-+/+(MRL/+) mice develop pancreatitis spontaneously by an autoimmune mechanism but only when they are more than 34 weeks old. Because this disease might be a model of multi-factorial diseases controlled by genetic and environmental factors, beginning at 6 weeks old, we injected polyinosinic:polycytidylic acid (poly I:C) into MRL/+ mice and in addtion, into MRL/Mp mice bearing the Fas deletion mutant gene, lpr (MRL/lpr). Poly I:C induced chronic severe pancreatitis in all the MRL/+ mice and to a lesser extent in the MRL/lpr mice by 18 weeks of age. There was no pancreatitis in control mice of both strains at the same age. Other than chronic pancreatitis, no severe autoimmune diseases were observed in MRL/+ mice. Immunohistochemical examinations revealed predominant infiltration of CD4⁺ T cells and Mac-2⁺ activated macrophages in the pancreatic lesions. Splenic expression of the mRNAs for TNF-α and IL-10, which is known to suppress the development of pancreatitis, were increased in both strains of mice. These findings suggest that an MRL strain of mice treated with poly I:C might be a good model for developing new approaches to the study of the pathogenesis of autoimmune pancreatitis.

Keywords: Fas Fas ligand IL-10 poly I:C TNF-α

Document Type: Research article

DOI: 10.1046/j.1365-2249.2002.01881.x

Affiliations: 1: Department of Oral and Maxillofacial Surgery, Tohoku University School of Dentistry, Sendai, and 2: Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan

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A novel autoimmune pancreatitis model in MRL mice treated with polyinosinic:polycytidylic acid