title: Hypoperfusion causes increased production of interleukin 6 and tumor necrosis factor alpha in the isolated, dually perfused placental cotyledon.
abstract: OBJECTIVE
  Our purpose was to determine whether exposure of the isolated, perfused human placental cotyledon to different fetal circuit perfusion rates, and to concomitant pressure differences, alters placental production of interleukin 6 and tumor necrosis factor alpha.
  
  
  METHODS
  The maternal and fetal circulations of 2 cotyledons from 5 placentas were perfused for 4 hours. The fetal circulation of 1 cotyledon was perfused at a low rate of 1 mL/min, and the other at a high rate of 10 mL/min. The maternal circulation of each cotyledon was perfused at 10 mL/min. Effluents from the fetal circulation were collected at hourly intervals, and concentrations of interleukin 6 and tumor necrosis factor alpha were determined by enzyme-linked immunosorbent assay. Concentrations of interleukin 6, obtained from a prior study with an estimated physiologic fetal circulation rate of 4 mL/min, were compared with the low and high perfusion rate results.
  
  
  RESULTS
  Concentrations of interleukin 6 and tumor necrosis factor alpha were greater at the perfusion rate of 1 mL/min, in comparison with the perfusion rate of 10 mL/min, with statistically significant differences achieved at 2 and 4 hours for interleukin 6 and at 4 hours for tumor necrosis factor alpha. Concentrations of both cytokines increased exponentially with time. Placental perfusion pressures were significantly greater at the perfusion rate of 10 mL/min.
  
  
  CONCLUSIONS
  Placental hypoperfusion results in an increased production of both interleukin 6 and tumor necrosis factor alpha. This finding links placental perfusion abnormalities to the myriad of disorders associated with elevated concentrations of inflammatory cytokines, including cerebral palsy.
authors.affiliation: Division of Maternal-Fetal Medicine, Madigan Army Medical Center, Tacoma, WA 98431, USA.
authors.forename: B T
authors.initials: BT
authors.lastname: Pierce
authors.forename: L M
authors.initials: LM
authors.lastname: Pierce
authors.forename: R K
authors.initials: RK
authors.lastname: Wagner
authors.forename: C C
authors.initials: CC
authors.lastname: Apodaca
authors.forename: R F
authors.initials: RF
authors.lastname: Hume
authors.forename: P E
authors.initials: PE
authors.lastname: Nielsen
authors.forename: B C
authors.initials: BC
authors.lastname: Calhoun
mesh_terms: D001775:Blood Circulation; D005260:Female; D005333:Fetus / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D009994:Osmolar Concentration; D010477:Perfusion / Q000379:methods; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D011312:Pressure; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha