中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (1): 47-50.doi: 10.4103/1673-5374.341044

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

白细胞介素1:围产期神经保护的重要靶点?

  

  • 出版日期:2023-01-15 发布日期:2022-06-16

Interleukin-1: an important target for perinatal neuroprotection?

Sharmony B. Kelly1, 2, Elys Green3, 4, Rod W. Hunt1, 3, 4, Claudia A. Nold-Petry1, 3, Alistair J. Gunn5, Marcel F. Nold1, 3, 4, #, #br# Robert Galinsky1, 2, *, #   

  1. 1The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia; 2Department of Obstetrics and Gynaecology, Monash University, Victoria, Australia;  3Department of Pediatrics, Monash University, Victoria, Australia; 4Monash Newborn, Monash Children’s Hospital, Melbourne, Australia; 5Department of Physiology, The University of Auckland, Auckland, New Zealand
  • Online:2023-01-15 Published:2022-06-16
  • Contact: Robert Galinsky, PhD, robert.galinsky@hudson.org.au.
  • Supported by:
    The work was supported by the CJ Martin Postdoctoral Fellowship and grants from the National Health and Medical Research Council of Australia (1090890 and 1164954), the Cerebral Palsy Alliance, Harold and Cora Brennen Benevolent Trust, Health Research Council of New Zealand (17/601) and the Victorian Government’s Operational Infrastructure Support Program (to RG).

摘要: https://orcid.org/0000-0002-6374-9372 (Robert Galinsky)

Abstract: Perinatal inflammation is a significant risk factor for lifelong neurodevelopmental impairments such as cerebral palsy. Extensive clinical and preclinical evidence links the severity and pattern of perinatal inflammation to impaired maturation of white and grey matters and reduced brain growth. Multiple pathways are involved in the pathogenesis of perinatal inflammation. However, studies of human and experimental perinatal encephalopathy have demonstrated a strong causative link between perinatal encephalopathy and excessive production of the pro-inflammatory effector cytokine interleukin-1. In this review, we summarize clinical and preclinical evidence that underpins interleukin-1 as a critical factor in initiating and perpatuating systemic and central nervous system inflammation and subsequent perinatal brain injury. We also highlight the important role of endogenous interleukin-1 receptor antagonist in mitigating interleukin-1-driven neuroinflammation and tissue damage, and summarize outcomes from clinical and mechanistic animal studies that establish the commercially available interleukin-1 receptor antagonist, anakinra, as a safe and effective therapeutic intervention. We reflect on the evidence supporting clinical translation of interleukin-1 receptor antagonist for infants at the greatest risk of perinatal inflammation and impaired neurodevelopment, and suggest a path to advance interleukin-1 receptor antagonist along the translational path for perinatal neuroprotection.

Key words: brain, inflammation, interleukin-1 receptor antagonist, interleukin-1, interleukin-1β, neonatal encephalopathy, neuroprotection, preterm brain injury