From the Third Department of Internal Medicine, Kansai Medical University, Moriguchi, Japan.
Pancreas. 2014 Jan;43(1):28-36. doi: 10.1097/MPA.0b013e3182a7c76b.
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.
尽管慢性酒精摄入是慢性胰腺炎的主要病因，但只有不到 10%的酗酒者会患上这种疾病。为了解决这个问题，我们创建了一种由酒精和脂多糖（LPS）诱导的胰腺炎小鼠模型，并分析了其免疫反应。
C57BL/6 小鼠饮用 20%乙醇（AL）水，并在 4 周内每周两次腹膜内注射 LPS。严重联合免疫缺陷小鼠用来自野生型小鼠的脾细胞、CD4 细胞或 CD8 T 细胞重建，然后进行类似处理。通过组织学评分来评估胰腺炎的严重程度，并测量血清细胞因子水平。
单独的乙醇不会引起胰腺炎。然而，给予 AL+LPS 或 LPS 本身会诱导胰腺炎。与 LPS 处理的小鼠相比，用 AL+LPS 处理的小鼠的组织学评分更高。AL+LPS 处理的小鼠血清中白细胞介素 1β、干扰素-γ 和肿瘤坏死因子-α 的水平升高。只有在用脾细胞、CD4 细胞或 CD8 T 细胞重建后，严重联合免疫缺陷小鼠才会发生胰腺炎。
固有免疫系统的反复刺激是引起胰腺炎所必需的，但不是充分的条件。获得性免疫反应的参与对于疾病的发展是必要的。
