Dr. Nardhy Gomez-Lopez’s paper “Blockade of IL-6R prevents preterm birth and adverse neonatal outcomes” was published in eBioMedicine.
Evidence before this study
Prematurity remains as the leading cause of neonatal morbidity and mortality before five years of age globally. One in every three preterm infants is born to a pregnant individual with inflammation of the amniotic cavity (i.e., intra-amniotic inflammation), which is diagnosed by elevated concentrations of IL-6 in amniotic fluid. Most cases of intra-amniotic inflammation occur in the absence of microbes, a condition that was recently termed sterile intra-amniotic inflammation. Despite its prevalence and severe consequences, to date there is no approved treatment for this devastating obstetrical disease. Tocilizumab, an anti-IL-6 receptor monoclonal antibody, has been successfully utilized in pregnant individuals with inflammatory conditions such as rheumatoid arthritis. The recent COVID-19 pandemic further demonstrated the successful use of the anti-IL-6 receptor monoclonal antibody to reduce the inflammatory phase of infection caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in pregnant patients, with no reported detrimental maternal or fetal effects. Yet, treatment of sterile intra-amniotic inflammation with an anti-IL-6 receptor monoclonal antibody has not been investigated.
Added value of this study
We applied a multidisciplinary approach including human data together with the development of an animal model of sterile intra-amniotic inflammation-induced preterm birth to show that the blockade of IL-6R in the mother prevents preterm birth and mitigates adverse neonatal outcomes. Moreover, we demonstrated that the beneficial effects of prenatal IL-6 receptor blockade extend to neonatal life, thereby avoiding the long-term consequences of in utero exposure to sterile intra-amniotic inflammation for the health of the offspring.
Implications of all the available evidence
This study demonstrates the previously untested application of IL-6 receptor blockade for the prevention of preterm birth and adverse neonatal outcomes driven by sterile intra-amniotic inflammation. Importantly, our findings from this clinically relevant animal model provide a proof-of-concept for undertaking future studies in larger animals, and eventually humans, using aIL-6R to prevent preterm birth and adverse neonatal outcomes.