@article{oai:twinkle.repo.nii.ac.jp:00018881, author = {FUKUYA, Yuji and NISHINO, Takayoshi and OYAMA, Hiroyasu and WATANABE, Shin-ichiro and HAYASHI, Naoaki}, issue = {3/4}, journal = {東京女子医科大学雑誌}, month = {Apr}, note = {[目的]Interleukin-10 (IL-10)は抗炎症性サイトカインとして知られており,セルレイン(Cn)やコリンデフィシエントを用いた実験膵炎モデルでIL-10を投与することで膵炎が改善するという報告がある.今回我々は,セルレインおよび,リポポリサッカライド(LPS)を用いたマウス壊死性膵炎モデルを作製し,IL-10の投与効果を検討した.[方法]マウスにLPS 10mg/kg1回(Cn初回投与時)腹腔内投与+Cn 50μg/kg 1時間毎に計10回腹腔内投与して膵炎を作製し,IL-10 10,000 UをCnおよびLPS初回投与1時間前より2時間毎に計7回投与し,その投与効果を検討した.[結果](1)血清膵酵素上昇はCn初回投与時より12,24時間後でIL-10投与により抑制された.(2)膵組織学的にCn初回投与時より12,24時間後でIL-10投与により空胞形成や壊死が軽減した.(3)分子生物学的にCn初回投与時より3,6,12,24時間後でIL-10投与により膵組織中のTNFα,IL-1βmRNAの発現が抑制された.[結論]IL-10は実験壊死性膵炎において,TNFα,IL-1βの産生を抑制し,重症化を軽減させると考えられた., Interleukin-10 (IL-10) has recently been identified as a major anti-inflammatory cytokine, and there have been several reports that IL-10 administration reduces severe necrosis in cerulein- or choline deficient (CDE) -induced pancreatitis. We investigated the effect of IL-10 in a mouse model of acute necrotizing pancreatitis induced by ten intraperitoneal infusion of cerulein (50 μg/kg) at hourly intervals and a single intraperitoneal injection of LPS (10 mg/kg) concomitant with the first cerulein injection. The IL-10 treated group was also injected with 10,000 U of IL-10 seven times intraperitoneally every 2 h beginning 1 h before the cerulein infusion. The pancreas was examined for histological changes and analyzed for tissue TNFα mRNA and IL-1β mRNA by RT-PCR. Serum amylase and lipase release peaked at 12 h after the first cerulein injection, but their concentrations at 12 and 24 h were significantly reduced by IL-10. Histologically, acinar cell necrosis and vacuolization were dramatically attenuated at 12 and 24 h in the IL-10 treated group, and induction of tissue TNFα mRNA and IL-1β mRNA in the pancreas was significantly reduced by IL-10. In conclusion, IL-10 is capable of decreasing the severity of experimental acute necrotizing pancreatitis. Inhibition of TNFα and IL-1β production in the pancreas may explain the protective effect of IL-10.}, pages = {78--87}, title = {Interleukin 10 Reduces the Severity of Acute Necrotizing Pancreatitis in Mice}, volume = {73}, year = {2003} }