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 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.