Effect of T helper cell 1/T helper cell 2 balance and nuclear factor-κB on white matter injury in premature neonates

Abstract

Incidence of white matter injury (WMI), which is featured as softening of white matter tissues, has recently increased. Previous studies have demonstrated a close correlation between T helper cell 1 and T helper cell 2 (Th1/Th2) imbalance and nuclear factor‑κB (NF‑κB) with brain disease. Their role in premature WMI, however, remains to be illustrated. Serum samples were collected from 60 premature WMI neonates, plus another control group of 60 premature babies without WMI. Patients were further divided into mild, moderate and severe WMI groups. Reverse transcription quantitative polymerase chain reaction was used to test mRNA expression levels of Th1/Th2 cytokines, including interleukin 2 (IL)‑2, tumor necrosis factor‑α (TNF‑α), IL‑4, IL‑10 and nuclear factor (NF)‑κB, whilst their serum levels were measured by ELISA. Their correlation with disease occurrence and progression were further analysed, to illustrate the effect of Th1/Th2 balance and NF‑κB on pathology of premature WMI. Serum levels of IL‑4 and IL‑10 were significantly decreased in premature WMI babies, whilst IL‑2, TNF‑α and NF‑κB were upregulated (P<0.05 vs. control group). With aggravated disease, IL‑4 and IL‑10 expression was further decreased while IL‑2, TNF‑α and NF‑κB were increased (P<0.05 vs. mild WMI group). Th1 cytokines IL‑2 and TNF‑α and NF‑κB were negatively correlated with Th2 cytokines IL‑4 and IL‑10. Disease severity was positively correlated with IL‑2, TNF‑α and NF‑κB expression, and was negatively correlated with IL‑4 and IL‑10 (P<0.05). Th1/Th2 imbalance and NF‑κB upregulation were observed in WMI pathogenesis, with elevated secretion of Th1 cytokines and decreased Th2 cytokines, suggesting that Th1/Th2 imbalance and NF‑κB upregulation may be a potential indicator for the early diagnosis and treatment of WMI pathogenesis and progression.

Altered distributions and functions of natural killer T cells and γδ T cells in neonates with neonatal encephalopathy, in school-age children at follow-up, and in children with cerebral palsy

“…However, we did not observe increases in the levels of Th1 or Th17 cytokines in the serum of NE patients, suggesting that T cell activation may be restricted to the brain. Future studies are required to determine if the numerical changes reflect movement of B cells and T cells to the brain or whether particular subsets of these cells, such as regulatory B cells (Bodhankar et al, 2013) or Th1, Th2, Th17 or regulatory T cells (Su et al, 2018), are numerically altered. Future studies are also required to determine if the increased numbers of B cells in patients with NE are associated with higher serum immunoglobulin levels.…”

Association Between Assisted Reproductive Technology and White Matter Injury in Premature Infants: A Case-Control Study

“…The placenta seems to be more vulnerable after ART treatment. Studies have shown that there is a significant increase in the expression of NFκB in ART placental tissue (19), and the upregulation of NFκB has been confirmed to be related to the pathogenesis of WMI (20,21). In addition, in the critical early period of brain development, fetal steroid hormones are believed to play a role in the epigenetic fetal programming mechanism.…”

The role of lymphocytes in neonatal encephalopathy

“…A study involving 60 white matter injury (WMI) premature neonates showed a correlation between low levels of IL-4 and IL-10 and high levels of IL-2, TNF-α and NF-κB activation with the severity of the injury. This imbalance in Th1/Th2 cytokine production along with the upregulation of NF-κB have been suggested as potential biomarkers for the early diagnosis and treatment of WMI in premature neonates ( Su et al., 2018 ). IL-6, IL-4, IL-12, and IL-17 are elevated in neonates with NE and neonatal arterial ischemic stroke (NAIS).…”