title: Melatonin attenuates acute pancreatitis-associated lung injury in rats by modulating interleukin 22.
abstract: OBJECTIVE
  To investigate whether therapeutic treatment with melatonin could protect rats against acute pancreatitis and its associated lung injury.
  
  
  METHODS
  Seventy-two male Sprague-Dawley rats were randomly divided into three groups: the sham operation (SO), severe acute pancreatitis (SAP), and melatonin treatment (MT) groups. Acute pancreatitis was induced by infusion of 1 mL/kg of sodium taurocholate (4% solution) into the biliopancreatic duct. Melatonin (50 mg/kg) was administered 30 min before pancreatitis was induced, and the severity of pancreatic and pulmonary injuries was evaluated 1, 4 and 8 h after induction. Serum samples were collected to measure amylase activities, and lung tissues were removed to measure levels of mRNAs encoding interleukin 22 (IL-22) and T helper cell 22 (Th22), as well as levels of IL-22.
  
  
  RESULTS
  At each time point, levels of mRNAs encoding IL-22 and Th22 were significantly higher (P < 0.001) in the MT group than in the SAP group (0.526 ± 0.143 vs 0.156 ± 0.027, respectively, here and throughout, after 1 h; 0.489 ± 0.150 vs 0.113 ± 0.014 after 4 h; 0.524 ± 0.168 vs 0.069 ± 0.013 after 8 h, 0.378 ± 0.134 vs 0.122 ± 0.015 after 1 h; 0.205 ± 0.041 vs 0.076 ± 0.019 after 4 h; 0.302 ± 0.108 vs 0.045 ± 0.013 after 8 h, respectively) and significantly lower (P < 0.001) in the SAP group than in the SO group (0.156 ± 0.027 vs 1.000 ± 0.010 after 1 h; 0.113 ± 0.014 vs 1.041 ± 0.235 after 4 h; 0.069 ± 0.013 vs 1.110 ± 0.213 after 8 h, 0.122 ± 0.015 vs 1.000 ± 0.188 after 1 h; 0.076 ± 0.019 vs 0.899 ± 0.125 after 4 h; 0.045 ± 0.013 vs 0.991 ± 0.222 after 8 h, respectively). The mean pathological scores for pancreatic tissues in the MT group were significantly higher (P < 0.01) than those for samples in the SO group (1.088 ± 0.187 vs 0.488 ± 0.183 after 1 h; 2.450 ± 0.212 vs 0.469 ± 0.242 after 4 h; 4.994 ± 0.184 vs 0.513 ± 0.210 after 8 h), but were significantly lower (P < 0.01) than those for samples in the SAP group at each time point (1.088 ± 0.187 vs 1.969 ± 0.290 after 1 h; 2.450 ± 0.212 vs 3.344 ± 0.386 after 4 h; 4.994 ± 0.184 vs 6.981 ± 0.301 after 8 h). The severity of SAP increased significantly (P < 0.01) over time in the SAP group (1.088 ± 0.187 vs 2.450 ± 0.212 between 1 h and 4 h after inducing pancreatitis; and 2.450 ± 0.212 vs 4.994 ± 0.184 between 4 and 8 h after inducing pancreatitis).
  
  
  CONCLUSIONS
  Melatonin protects rats against acute pancreatitis-associated lung injury, probably through the upregulation of IL-22 and Th22, which increases the innate immunity of tissue cells and enhances their regeneration.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, Zhejiang Province, China.
authors.forename: Jia-Ping
authors.initials: JP
authors.lastname: Huai
authors.forename: Xue-Cheng
authors.initials: XC
authors.lastname: Sun
authors.forename: Meng-Jun
authors.initials: MJ
authors.lastname: Chen
authors.forename: Yin
authors.initials: Y
authors.lastname: Jin
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Ye
authors.forename: Jian-Sheng
authors.initials: JS
authors.lastname: Wu
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Huang
mesh_terms: D000208:Acute Disease; D055371:Acute Lung Injury / Q000188:drug therapy*; D000681:Amylases / Q000097:blood; D000818:Animals; D007113:Immunity, Innate; D007378:Interleukins / Q000502:physiology*; D008168:Lung / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D010195:Pancreatitis / Q000150:complications* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097043:Interleukin-22
chemical_list: D000681:Amylases; D007378:Interleukins; D008550:Melatonin; D000097043:Interleukin-22