title: Effect of interleukin-6 receptor blockade on feto-maternal outcomes in a rat model of intrauterine inflammation.
abstract: OBJECTIVE
  To study the effect of blocking the inflammatory cascade with interleukin-6 receptor antibody (anti-IL-6R) on feto-maternal outcomes in a rat model.
  
  
  METHODS
  Pregnant Sprague-Dawley rats (n = 38) were injected intraperitoneally (day 22) (control, anti-IL-6R 30 μg/kg, lipopolysaccharide [LPS] 250 μg/kg or 500 μg/kg alone or combined with anti-IL-6R) followed by preterm caesarian performed 12 h later. Resuscitated pups (n = 179) were given to surrogate mothers. Primary outcomes were maternal and pup mortality.
  
  
  RESULTS
  Fifty percent of pregnant rats died after LPS 500 μg/kg + anti-IL-6R injection but none in other groups. Neonatal mortality at 24 h was 63% and 86% in LPS 500 μg/kg and LPS 500 μg/kg + anti-IL-6R groups, respectively (P < 0.05). Surviving pups in the latter group presented a severe growth deficit compared to the LPS 500 μg/kg group (P < 0.01) and showed no difference with controls for open field testing. Maternal cytokine analysis after LPS 500 μg/kg + anti-IL-6R injection showed a tendency for increased IL-1 production (P = 0.06).
  
  
  CONCLUSIONS
  Paradoxically, the association of pregnancy, inflammation and anti-IL-6R increases the inflammatory effects of LPS.
authors.affiliation: Department of Obstetrics and Gynecology, CHUS and Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Justine
authors.initials: J
authors.lastname: Ouellet
authors.forename: Maryse
authors.initials: M
authors.lastname: Berthiaume
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Corriveau
authors.forename: Marek
authors.initials: M
authors.lastname: Rola-Pleszczynski
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Pasquier
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D002821:Chorioamnionitis / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D019947:Receptors, Interleukin-6
keywords: fetal growth deficit; inflammation; maternal mortality; neurodevelopmental assessment; preterm birth; rat model.