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.
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.
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.
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.