Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China.
Biomed Pharmacother. 2012 Mar;66(2):83-8. doi: 10.1016/j.biopha.2011.11.017. Epub 2012 Jan 9.
Chronic pancreatitis is a progressive inflammatory disease featuring irreversible irregular scarring of the exocrine parenchyma characterized by acinar destruction and fibrosis subsequent to inflammation in the pancreas. Despite decades of research, the knowledge is limited to the treatment of this disease. After finding a connection between interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1Ra) in caerulein-induced chronic pancreatitis, we assumed that recombinant human IL-1Ra (rhIL-1Ra), the natural antagonist of IL-1β, might have a protective role in chronic pancreatitis in mice. Chronic pancreatitis was induced by repetitive intraperitoneal injections of caerulein in C57/BL mice followed by a consecutive administration of rhIL-1Ra (10mg/kg). Collagen content and histological changes in the pancreas as well as serum amylase and lipase were measured. We found that rhIL-1Ra significantly decreased the hydroxyproline and the fibrotic area in the pancreas after the caerulein challenge. Caerulein-induced serum amylase elevation and tissue damage were also attenuated in rhIL-1Ra treated mice. Our results reveal a potential role of rhIL-1Ra in protecting mice against caerulein-induced chronic pancreatitis and lead to a conclusion that this protein may be a potential candidate agent for the treatment of chronic pancreatitis in humans.
慢性胰腺炎是一种进行性炎症性疾病，其特征为胰腺炎症后外分泌实质发生不可逆的不规则瘢痕形成，表现为腺泡破坏和纤维化。尽管经过数十年的研究，我们对这种疾病的认识仍然有限。在发现白细胞介素-1β (IL-1β) 和白细胞介素-1 受体拮抗剂 (IL-1Ra) 与胆酸钠诱导的慢性胰腺炎之间的联系后，我们假设重组人 IL-1Ra (rhIL-1Ra)，IL-1β 的天然拮抗剂，可能在慢性胰腺炎小鼠中具有保护作用。通过在 C57/BL 小鼠中重复腹腔内注射胆酸钠并随后连续给予 rhIL-1Ra（10mg/kg）来诱导慢性胰腺炎。测量胰腺中的胶原含量和组织学变化以及血清淀粉酶和脂肪酶。我们发现，rhIL-1Ra 在胆酸钠攻击后显著降低了胰腺中的羟脯氨酸和纤维化面积。rhIL-1Ra 处理的小鼠中，胆酸钠诱导的血清淀粉酶升高和组织损伤也得到了缓解。我们的结果揭示了 rhIL-1Ra 在保护小鼠免受胆酸钠诱导的慢性胰腺炎中的潜在作用，并得出结论，该蛋白可能是治疗人类慢性胰腺炎的潜在候选药物。
