Effect of interleukin-6 receptor blockade on feto-maternal outcomes in a rat model of intrauterine inflammation

• Published in: The journal of obstetrics and gynaecology research Vol. 39; no. 10; pp. 1456 - 1464
• Main Authors: Ouellet, Justine, Berthiaume, Maryse, Corriveau, Stéphanie, Rola-Pleszczynski, Marek, Pasquier, Jean-Charles
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01.10.2013
• Subjects: Animals; Animals, Newborn - growth & development; Chorioamnionitis - metabolism; Cytokines - metabolism; Disease Models, Animal; Female; fetal growth deficit; inflammation; Injections, Intraperitoneal; Lipopolysaccharides; maternal mortality; neurodevelopmental assessment; Pregnancy; preterm birth; rat model; Rats; Rats, Sprague-Dawley; Receptors, Interleukin-6 - antagonists & inhibitors; Receptors, Interleukin-6 - metabolism; preterm birth; rat model; neurodevelopmental assessment; inflammation; maternal mortality; fetal growth deficit
• ISSN: 1341-8076; 1447-0756; 1447-0756
• DOI: 10.1111/jog.12089

Aim 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). Conclusion Paradoxically, the association of pregnancy, inflammation and anti‐IL‐6R increases the inflammatory effects of LPS.