Serum cytokine profiling in neonates with hypoxic ischemic encephalopathy

Go, H.,* Saito, Y., Maeda, H., Maeda, R., Yaginuma, K., Ogasawara, K., Kashiwabara, N., Kawasaki, Y., Hosoya, M. | JNPM 2021;


BACKGROUND:The fetal brain is vulnerable to severe and sustained hypoxia during and after birth, which can lead to hypoxic-ischemic encephalopathy (HIE). HIE is characterized by clinical and laboratory evidence of acute or subacute brain injury. The role of cytokines in the pathogenesis of brain injury and their relation to neurological outcomes of asphyxiated neonates are not fully understood. In this study, we investigated cytokine profile related to cerebral palsy (CP) with neonatal hypoxic ischemic encephalopathy (HIE) and HIE severity.

METHODS:Eligible subjects were HIE newborns with a gestational age between 36 and 42 weeks. We included newborns who was born at our NICU and did not admit to NICU as healthy controls. The study comprised 52 newborns, including 13 with mild to severe HIE and 39 healthy control. Serum cytokine profiles were performed using a LUMINEX cytokine kit (R&D Systems).

RESULTS:VEGF, MCP-1, IL-15, IL-12p70, IL-12p40, IL-1Ra, IL-2, IL-6, IL-7, IL-8, IL-10, IFN-γ, G-CSF and eotaxin in the HIE patients were significantly increased compared with the healthy neonates. In the subgroup analysis, IL-6 and G-CSF were significantly increased in CP infants (n = 5) compared with non-CP infants (n = 8). Five and eight HIE patients were classified into the mild HIE and moderate-severe HIE groups, respectively. IL-6, 10, 1Ra, and G-CSF in the moderate-severe HIE group were significantly higher than those in the mild HIE group.

CONCLUSION:We demonstrated that higher serum IL-6 and G-CSF at birth in HIE patients were associated with CP and moderate-severe HIE.

*Corresponding Author: 

Hayato Go, M.D. PhD., Departments of Pediatrics, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Japan. Tel.: +81 247 1563; E-mail: