The role of innate immunity in the pathogenesis of experimental autoimmune pancreatitis in mice

Abstract

Objective: To determine the role of innate immunity in the development of autoimmune pancreatitis in mice induced by toll-like receptor (TLR) stimulation.

Methods: Six-week-old female MRL/Mp mice were injected intraperitoneally with polyinosinic polycytidylic acid (poly I:C) or lipopolysaccharide (LPS) at doses of 5 mg/kg body weight twice weekly for 12 weeks. The mice were killed, and the severity of pancreatitis was graded using a histological scoring system. Serum cytokine levels of mice with pancreatitis and mice that were given a single injection of TLR ligands were measured using enzyme-linked immunosorbent assays. The effect of TLR stimulation on the development of pancreatitis was also examined using C57BL/6 interleukin (IL)-10-deficient mice.

Results: Administration of poly I:C accelerated the development of pancreatitis in MRL/Mp mice, but LPS did not. Serum levels of IL-10 and IL-12 were significantly elevated in mice with autoimmune pancreatitis. A single injection of LPS markedly increased serum levels of interferon-γ, tumor necrosis factor-α, IL-10, and IL-12 compared with those of poly I:C-treated mice. Treatment with not only poly I:C but also LPS induced pancreatitis in IL-10-deficient mice but not in wild-type mice.

Conclusion: Repeated stimulation of innate immunity induces autoimmunity in the pancreas of mice via an imbalance between proinflammatory and anti-inflammatory cytokines.