Acquired Immunity Plays an Important Role in the Development of Murine Experimental Pancreatitis Induced by Alcohol and Lipopolysaccharide

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 1&bgr;, interferon-&ggr;, and tumor necrosis factor &agr; 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.

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