title: Acquired immunity plays an important role in the development of murine experimental pancreatitis induced by alcohol and lipopolysaccharide.
abstract: OBJECTIVE
  Although chronic alcohol ingestion is the major cause of chronic pancreatitis, less than 10% of alcohol abusers develop this disease. To address this issue, we created a murine model of pancreatitis induced by alcohol and lipopolysaccharide (LPS) and analyzed its immune responses.
  
  
  METHODS
  C57BL/6 mice were administered 20% ethanol (AL) in their drinking water and then injected intraperitoneally with LPS twice weekly for 4 weeks. Severe combined immunodeficient mice were reconstituted with splenocytes, CD4 cells, or CD8 T cells isolated from wild-type mice and then treated similarly. The severity of pancreatitis was graded histologically, and serum cytokine levels were measured.
  
  
  RESULTS
  Ethanol alone did not cause pancreatitis. However, the administration of AL+LPS or LPS alone induced pancreatitis. The histological scores were higher in the mice treated with AL+LPS than in those treated with LPS. Serum levels of interleukin 1β, interferon-γ, and tumor necrosis factor α were elevated in the AL+LPS-treated mice. The severe combined immunodeficient mice developed pancreatitis only after their reconstitution with splenocytes, CD4 cells, or CD8 T cells.
  
  
  CONCLUSIONS
  Repeated stimulation of the innate immune system is necessary, but not sufficient, to cause pancreatitis. The participation of the acquired immune response is essential for the development of the disease.
authors.affiliation: From the Third Department of Internal Medicine, Kansai Medical University, Moriguchi, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakayama
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishio
authors.forename: Masao
authors.initials: M
authors.lastname: Yamashina
authors.forename: Takashi
authors.initials: T
authors.lastname: Okazaki
authors.forename: Yutaku
authors.initials: Y
authors.lastname: Sakaguchi
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yoshida
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fukui
authors.forename: Kazushige
authors.initials: K
authors.lastname: Uchida
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Okazaki
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004357:Drug Synergism; D000431:Ethanol; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D053583:Interleukin-1beta / Q000097:blood / Q000276:immunology; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D010179:Pancreas / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D012720:Severity of Illness Index; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D007371:Interferon-gamma