title: Recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) attenuates caerulein-induced chronic pancreatitis in mice.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China.
authors.forename: Jiaqing
authors.initials: J
authors.lastname: Shen
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Xiang
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Lan
authors.initials: L
authors.lastname: Qian
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yang
authors.forename: Shunying
authors.initials: S
authors.lastname: Zhu
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Xingpeng
authors.initials: X
authors.lastname: Wang
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D002108:Ceruletide / Q000633:toxicity; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D007274:Injections, Intraperitoneal; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D008049:Lipase / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050500:Pancreatitis, Chronic / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D002108:Ceruletide; D003094:Collagen; D008049:Lipase; D000681:Amylases; D006909:Hydroxyproline