title: Omega-3 polyunsaturated fatty acids inhibit the increase in cytokines and chemotactic factors induced in vitro by lymph fluid from an intestinal ischemia-reperfusion injury model.
abstract: OBJECTIVE
  To investigate the active factors and the intervention effect of ω-3 polyunsaturated fatty acids (PUFAs) during intestinal ischemia-reperfusion (I/R) injury, which causes the inflammation of monocytes-macrophages cultured in lymph fluid and stimulated with ω-3 PUFAs.
  
  
  METHODS
  Forty-eight Sprague-Dawley male rats were randomly divided into the following two groups: A. (N + D) group and B. (I/R + D) group. The rats in the (N + D) group were drained of lymph for 180 min; the rats in the (I/R + D) group were subjected to 60 min ischemia by clamping the superior mesenteric artery followed by 120 min reperfusion and 180 min of lymph draining. Lymph fluid from each group was further divided into 4 subgroups, respectively: lymph group (A1, B1); eicosopentaenoic acid (EPA)-treated group (A2, B2); EPA + docosahexaeonic acid (DHA)-treated group (A3, B3); and DHA-treated group (A4, B4), then cultured monocyte-macrophage cell line.
  
  
  RESULTS
  The levels of tumor necrosis factor-α, interleukin (IL)-1 β, IL-6, soluble cell adhesion molecule-1, chemotactic factors macrophage chemoattractant protein-1, macrophage inflammatory protein-2, and high mobility group box protein 1 in the B1 group were significantly higher than in the A1 group. Importantly, addition of EPA, EPA + DHA, and DHA to the culture media significantly reduced the levels of the above-mentioned factors. Cell stimulation with EPA, EPA + DHA, and DHA also significantly decreased the expression of Toll-like receptor 4, nuclear factor-κB p65, macrophage chemoattractant protein-1, and macrophage inflammatory protein-2 with the combined treatment of EPA and DHA showing the strongest effect.
  
  
  CONCLUSIONS
  The factors induced in lymph during intestinal I/R injury can cause inflammation in vitro. These data provide in vitro evidence that ω-3 PUFAs provide a protective effect by reducing the inflammatory response caused by intestinal I/R lymph. Moreover, the synergism of EPA and DHA had the greatest effect, which is possibly mediated through Toll-like receptor 4 and nuclear factor-κB p65.
authors.affiliation: Department of Parenteral and Enteral Nutrition, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Parenteral and Enteral Nutrition, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: Hgzpumc@163.com.
authors.forename: Gui-zhen
authors.initials: GZ
authors.lastname: He
authors.affiliation: Department of Parenteral and Enteral Nutrition, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yu-kang
authors.initials: YK
authors.lastname: Wang
authors.affiliation: Department of Parenteral and Enteral Nutrition, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Kai-guo
authors.initials: KG
authors.lastname: Zhou
authors.affiliation: Department of Parenteral and Enteral Nutrition, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: En-ling
authors.initials: EL
authors.lastname: Ma
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D015118:Eicosapentaenoic Acid / Q000494:pharmacology / Q000627:therapeutic use; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008196:Lymph / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D002630:Chemotactic Factors; D016207:Cytokines; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
keywords: DHA; EPA; Intestinal lymph drainage; Ischemia reperfusion; NF-κB p65