Serum cytokine profiling in neonates with hypoxic ischemic encephalopathy

Abstract

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 o 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.

The NESHIE and CP Genetics Resource (NCGR): A database of genes and variants reported in neonatal encephalopathy with suspected hypoxic ischemic encephalopathy (NESHIE) and consequential cerebral palsy (CP)

“…In support of the latter, the NESHIE- and CP-associated variants, IL1B rs16944 and IL6 rs1800795 catalogued in NCGR are associated with increased expression of their respective pro-inflammatory cytokines, IL1B and IL6 [ 56 , [116] , [117] , [118] , [119] , [120] ]. These cytokines have been associated with inflammation and adverse clinical outcomes in NESHIE patients [ [121] , [122] , [123] ]. Thus, variants in IL1B and IL6 may underlie a genetic basis for inflammation in some patients with severe NESHIE.…”

Application of simple head cooling combined with gangliosides in neonatal hypoxic-ischemic encephalopathy

“…A few minutes after hypoxia and ischemia, the levels of IL-6 and other inflammatory cytokines increase rapidly, by inducing neuronal apoptosis and increasing toxic factors. Nitric oxide levels promote hypoxic-ischemic brain damage [15] . Hypocalcemia is a common disease of HIE.…”

Rationale for the Use of Cord Blood in Hypoxic-Ischaemic Encephalopathy

“…Recently, an increasing number of publications have described the prognostic role of markers of brain injury associated with HIE [ 123 – 126 ]. However, to date, although some studies have described the predictive value of the interleukin profile or metabolic parameters [ 127 – 129 ], no single marker has demonstrated sufficient reliability and reproducibility to be used as a biomarker or therapeutic target in a clinical setting even at the epigenetic level [ 130 ]. So far, the greatest area under the curve (0.96) resulted in a model which combines clinical signs with lactate and alanine levels [ 131 ].…”