Comparative Study on Experimental Autoimmune Pancreatitis and Its Extrapancreatic Involvement in Mice

Abstract

Objective 

The objective of the study was to study the relationship between autoimmune pancreatitis (AIP) and colitis in C57BL/6 interleukin 10–deficient (IL-10KO) mice and to compare the extrapancreatic involvement of AIP between IL-10KO and MRL/Mp mice that developed pancreatitis.

Methods 

Six-week-old female IL-10KO and MRL/Mp mice were injected intraperitoneally with polyinosinic polycytidylic acid (poly I:C) twice weekly for 8 or 12 weeks, respectively. The mice were killed, and the severity of inflammation in the pancreas, colon, liver, bile duct, and salivary gland was assessed using histological scoring systems. T-cell subsets derived from IL-10KO mice with pancreatitis were adoptively transferred into recombination activating gene 2–deficient mice.

Results 

Administration of poly I:C induced pancreatitis and accelerated the development of colitis in IL-10KO mice. Pancreatitis was characterized by specific destruction of exocrine glands and the production of various autoantibodies. Involvement of the liver and bile duct was observed in both IL-10KO and MRL/Mp mice, but sialadenitis was present only in MRL/Mp mice. Adoptive transfer of CD4⁺ T cells from AIP mice induced pancreatitis in recipient mice.

Conclusions 

Pancreatitis in IL-10KO mice resembles human type 1 AIP and is not associated with colitis. Genetic background may affect susceptibility to extrapancreatic involvement in type 1 AIP.