Recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) attenuates caerulein-induced chronic pancreatitis in mice
Recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) attenuates caerulein-induced chronic pancreatitis in mice
复制标题
重组人白细胞介素 1 受体拮抗剂 (rhIL-1Ra) 可减轻雨蛙素诱导的小鼠慢性胰腺炎
DOI：
10.1016/j.biopha.2011.11.017
复制
发表时间：
2012-03-01
影响因子：
7.5
通讯作者：
Wang, Xingpeng
中科院分区：
文献类型：
--
作者：
Shen, Jiaqing;Gao, Jing;Wang, Xingpeng
慢性胰腺炎是一种进行性炎性疾病，以胰腺炎症后的腺泡破坏和纤维化为特征，外分泌实质形成不可逆的不规则瘢痕。尽管经过了几十年的研究，人们对这种疾病的了解还是有限的。在发现白细胞介素-1 β (IL-1 β)和白细胞介素-1受体拮抗剂（IL-1Ra）在caerulein诱导的慢性胰腺炎中的联系后，我们假设IL-1 β的天然拮抗剂重组人IL-1Ra （rhIL-1Ra）可能在小鼠慢性胰腺炎中具有保护作用。在C57/BL小鼠腹腔内反复注射小蛋白，然后连续给予rhIL-1Ra (10 mg/kg)，诱导慢性胰腺炎。测定胰腺组织中胶原蛋白含量、组织学变化及血清淀粉酶、脂肪酶水平。我们发现rhIL-1Ra显著降低了小蛋白攻击后胰腺的羟脯氨酸和纤维化区域。rhIL-1Ra处理的小鼠血清淀粉酶升高和组织损伤也有所减轻。我们的研究结果揭示了rhIL-1Ra在保护小鼠免受小蛋白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。(c) 2012年Elsevier Masson SAS。版权所有。
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-1 beta (IL-1 beta) 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-1 beta, 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 (10 mg/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. (c) 2012 Elsevier Masson SAS. All rights reserved.