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

Abstract

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 30μg/kg, lipopolysaccharide [LPS] 250μg/kg or 500μg/kg alone or combined with anti-IL-6R) followed by preterm caesarian performed 12h 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 500μg/kg+anti-IL-6R injection but none in other groups. Neonatal mortality at 24h was 63% and 86% in LPS 500μg/kg and LPS 500μg/kg+anti-IL-6R groups, respectively (P<0.05). Surviving pups in the latter group presented a severe growth deficit compared to the LPS 500μg/kg group (P<0.01) and showed no difference with controls for open field testing. Maternal cytokine analysis after LPS 500μg/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. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.