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

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 P regnant S prague– D awley 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 .