Interleukin-1: an important target for perinatal neuroprotection?

Area of Science:

• Neuroscience
• Immunology
• Developmental Biology

Background:

• Perinatal inflammation is a major cause of lifelong neurodevelopmental impairments, including cerebral palsy.
• Inflammation impacts white and grey matter maturation and brain growth.
• Excessive interleukin-1 (IL-1) production is strongly linked to perinatal encephalopathy and brain injury.

Purpose of the Study:

• To review evidence on IL-1's role in perinatal brain injury.
• To highlight the protective function of IL-1 receptor antagonist.
• To evaluate anakinra as a therapeutic intervention for perinatal neuroprotection.

Main Methods:

• Systematic review of clinical and preclinical studies.
• Analysis of human and experimental perinatal encephalopathy models.
• Examination of mechanistic animal studies and clinical trial outcomes.

Main Results:

• IL-1 is a critical initiator and perpetuator of neuroinflammation and perinatal brain injury.
• Endogenous IL-1 receptor antagonist mitigates IL-1-driven neuroinflammation and tissue damage.
• Anakinra, a commercially available IL-1 receptor antagonist, is safe and effective in preclinical and clinical settings.

Conclusions:

• IL-1 receptor antagonist therapy, specifically anakinra, holds significant potential for perinatal neuroprotection.
• Further clinical translation is warranted for infants at high risk of perinatal inflammation and neurodevelopmental impairment.
• Targeting IL-1 pathways offers a promising strategy to prevent lifelong neurodevelopmental deficits.