title: 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.
  
  
  CONCLUSIONS
  Repeated stimulation of innate immunity induces autoimmunity in the pancreas of mice via an imbalance between proinflammatory and anti-inflammatory cytokines.
authors.affiliation: Third Department of Internal Medicine, Kansai Medical University, Moriguchi, Japan. nishioa@takii.kmu.ac.jp
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishio
authors.forename: Masanori
authors.initials: M
authors.lastname: Asada
authors.forename: Kazushige
authors.initials: K
authors.lastname: Uchida
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fukui
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Okazaki
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology; D005260:Female; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000502:physiology; D018664:Interleukin-12 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D010195:Pancreatitis / Q000209:etiology* / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics
chemical_list: D051193:Toll-Like Receptors; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma