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

Authors

  • Justine Ouellet,

    1. Department of Obstetrics and Gynecology, CHUS and Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Maryse Berthiaume,

    1. Department of Obstetrics and Gynecology, CHUS and Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Stéphanie Corriveau,

    1. Department of Physiology and Biophysics, CHUS and Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Marek Rola-Pleszczynski,

    1. Department of Pediatrics/Immunology, CHUS and Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Jean-Charles Pasquier

    Corresponding author
    • Department of Obstetrics and Gynecology, CHUS and Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Conflict of interest: None.
  • This paper was presented orally at the SMFM 31th Annual Pregnancy Meeting, 7–12 February 2011 San Francisco, California, USA.

Reprint request to: Dr Jean-Charles Pasquier, Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue North, J1H 5N4 Sherbrooke, QC, Canada. Email: jean-charles.pasquier@usherbrooke.ca

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.

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